1 00:00:05,120 --> 00:00:10,680 WELCOME TO THE SIXTH INSTALLMENT 2 00:00:10,680 --> 00:00:13,200 OF THE 21ST YEAR OF DEMYSTIFYING 3 00:00:13,200 --> 00:00:16,240 MEDICINE, THE COURSE WHOSE GOAL 4 00:00:16,240 --> 00:00:19,600 IS TO BRIDGE EXCITING 5 00:00:19,600 --> 00:00:20,880 DEVELOPMENTS IN BIOLOGY AND 6 00:00:20,880 --> 00:00:22,600 ENGINEERING WITH MEDICINE. 7 00:00:22,600 --> 00:00:25,600 I'M DAN KASTNER, I AM THE 8 00:00:25,600 --> 00:00:26,440 SCIENTIFIC DIRECTOR EMERITUS OF 9 00:00:26,440 --> 00:00:30,120 THE NATIONAL HUMAN GENOME 10 00:00:30,120 --> 00:00:31,720 RESEARCH INSTITUTE AND I WILL BE 11 00:00:31,720 --> 00:00:33,000 YOUR HOST THIS AFTERNOON. 12 00:00:33,000 --> 00:00:35,320 THE USUAL HOST AND FATHER OF THE 13 00:00:35,320 --> 00:00:44,720 COURSE, DR. ARIAS, HAS ASKED ME 14 00:00:44,720 --> 00:00:45,960 TO FILL IN FOR HIM. 15 00:00:45,960 --> 00:00:47,360 THE PURPOSE OF THIS COURSE IS TO 16 00:00:47,360 --> 00:00:48,360 ESTABLISH A DIALOGUE BETWEEN THE 17 00:00:48,360 --> 00:00:49,560 WORLDS OF BIOLOGY AND 18 00:00:49,560 --> 00:00:50,560 ENGINEERING AND MEDICINE, AND 19 00:00:50,560 --> 00:00:54,320 THAT DIALOGUE CRACKLES EVERY 20 00:00:54,320 --> 00:00:56,680 TUESDAY AFTERNOON FROM 4:00 TO 21 00:00:56,680 --> 00:01:00,440 6:00 IN THE AFTERNOON FROM 22 00:01:00,440 --> 00:01:01,600 JANUARY 4TH TO MAY THE THIRD. 23 00:01:01,600 --> 00:01:03,320 I'D LIKE TO JUST SHOW 24 00:01:03,320 --> 00:01:06,480 YOU A PICTURE TAKEN BY 25 00:01:06,480 --> 00:01:08,120 DR. ARIAS' GRANDFATHER, WITH A 26 00:01:08,120 --> 00:01:09,120 BOX CAMERA, OF THE CONSTRUCTION 27 00:01:09,120 --> 00:01:10,400 OF THE BROOKLYN BRIDGE. 28 00:01:10,400 --> 00:01:11,840 AND FOR THOSE OF YOU WHO DON'T 29 00:01:11,840 --> 00:01:14,320 KNOW, THE BROOKLYN BRIDGE GOES 30 00:01:14,320 --> 00:01:16,320 FROM MANHATTAN IN NEW YORK TO 31 00:01:16,320 --> 00:01:18,880 BROOKLYN, AND IT WAS BUILT 32 00:01:18,880 --> 00:01:20,920 BETWEEN 1869 AND 1883. 33 00:01:20,920 --> 00:01:25,120 AND HERE YOU SEE IN THIS PICTURE 34 00:01:25,120 --> 00:01:27,120 ACTUALLY TWO MEN WHO ARE ON A 35 00:01:27,120 --> 00:01:27,600 CATWALK. 36 00:01:27,600 --> 00:01:29,120 YOU CAN SEE TO THE LEFT. 37 00:01:29,120 --> 00:01:31,200 ONE OF THEM WALKED OVER FROM 38 00:01:31,200 --> 00:01:33,080 BROOKLYN AND THE OTHER FROM THE 39 00:01:33,080 --> 00:01:34,560 MANHATTAN SIDE, AND THEY'RE 40 00:01:34,560 --> 00:01:37,080 ACTUALLY HAVING A DISCUSSION 41 00:01:37,080 --> 00:01:40,720 ABOUT THE CHOLERA PANDEMIC OF 42 00:01:40,720 --> 00:01:40,920 1873. 43 00:01:40,920 --> 00:01:43,320 AGAIN, IN THE TRADITION OF 44 00:01:43,320 --> 00:01:44,800 BRINGING TOGETHER BASIC SCIENCES 45 00:01:44,800 --> 00:01:46,520 WITH CLINICAL MEDICINE. 46 00:01:46,520 --> 00:01:48,840 WELL, ON THE NEXT SLIDE, YOU 47 00:01:48,840 --> 00:01:50,120 WILL SEE WHAT WE HAVE IN STORE 48 00:01:50,120 --> 00:01:52,400 FOR US THIS AFTERNOON. 49 00:01:52,400 --> 00:01:55,800 TWO STELLAR TALKS. 50 00:01:55,800 --> 00:01:58,640 FIRST IS A TALK ENTITLED 51 00:01:58,640 --> 00:01:59,520 EPIGENETIC CONTRIBUTION TO 52 00:01:59,520 --> 00:02:01,920 SYSTEMIC LUPUS ERYTHEMATOSUS, 53 00:02:01,920 --> 00:02:04,200 AND OUR SPEAKER WILL BE 54 00:02:04,200 --> 00:02:05,800 DR. LINDSEY CRISWELL, WHO IS 55 00:02:05,800 --> 00:02:07,920 CURRENTLY THE DIRECTOR OF THE 56 00:02:07,920 --> 00:02:09,360 NATIONAL INSTITUTE OF ARTHRITIS 57 00:02:09,360 --> 00:02:11,320 AND MUSCULOSKELETAL AND SKIN 58 00:02:11,320 --> 00:02:13,480 DISEASES, AND SHE HAS A RESEARCH 59 00:02:13,480 --> 00:02:17,000 LAB IN THE GENOME INSTITUTE, IN 60 00:02:17,000 --> 00:02:19,600 THE GENOMICS OF AUTOIMMUNE 61 00:02:19,600 --> 00:02:20,320 RHEUMATIC DISEASES SECTION OF 62 00:02:20,320 --> 00:02:21,280 THE GENOME INSTITUTE. 63 00:02:21,280 --> 00:02:25,040 BEFORE SHE CAME TO THE NIH, SHE 64 00:02:25,040 --> 00:02:26,160 WAS THE VICE CHANCELLOR OF 65 00:02:26,160 --> 00:02:28,520 RESEARCH AT UCSF MEDICAL SCHOOL. 66 00:02:28,520 --> 00:02:31,760 SHE GOT HER MEDICAL DEGREE AT 67 00:02:31,760 --> 00:02:34,320 UCSF, HER MPH AT BERKLEY, AND A 68 00:02:34,320 --> 00:02:37,040 DOCTOR OF SCIENCES DEGREE IN 69 00:02:37,040 --> 00:02:38,240 GENETIC EPIDEMIOLOGY AT THE 70 00:02:38,240 --> 00:02:40,960 NETHERLANDS INSTITUTE FOR HEALTH 71 00:02:40,960 --> 00:02:42,960 SCIENCES IN ROTTERDAM. 72 00:02:42,960 --> 00:02:44,360 A FEW YEARS AGO, SHE WAS THE 73 00:02:44,360 --> 00:02:47,080 HENRY KUNKEL YOUNG INVESTIGATOR 74 00:02:47,080 --> 00:02:48,400 AWARD WINNER AND MORE RECENTLY 75 00:02:48,400 --> 00:02:49,320 WAS INDUCTED INTO THE 76 00:02:49,320 --> 00:02:49,960 ASSOCIATION OF AMERICAN 77 00:02:49,960 --> 00:02:51,560 PHYSICIANS. 78 00:02:51,560 --> 00:02:53,200 HER RESEARCH WORK CONCENTRATES 79 00:02:53,200 --> 00:02:55,840 ON GENOME-WIDE ASSOCIATION 80 00:02:55,840 --> 00:02:58,280 STUDIES OF LUPUS, RHEUMATOID 81 00:02:58,280 --> 00:03:00,880 ARTHRITIS AND SJOGREN'S 82 00:03:00,880 --> 00:03:01,960 SYNDROME, EPIGENETIC SIGNATURES 83 00:03:01,960 --> 00:03:03,520 OF INFLAMMATION AND AUTOIMMUNE 84 00:03:03,520 --> 00:03:04,920 DISEASE AND HEALTH DISPARITIES 85 00:03:04,920 --> 00:03:07,720 IN THE AUTOIMMUNE DISEASES. 86 00:03:07,720 --> 00:03:12,040 AND AS A SPECIAL TREAT TODAY, 87 00:03:12,040 --> 00:03:13,080 DR. CRISWELL IS GOING TO BE 88 00:03:13,080 --> 00:03:14,080 INTERVIEWING A PATIENT DURING 89 00:03:14,080 --> 00:03:15,320 HER PRESENTATION. 90 00:03:15,320 --> 00:03:16,600 MY COLLEAGUE GOT A LITTLE BIT 91 00:03:16,600 --> 00:03:18,040 AHEAD OF THINGS THERE WHEN I 92 00:03:18,040 --> 00:03:19,400 CLAPPED MY HAND. 93 00:03:19,400 --> 00:03:20,880 BUT NOW I'LL CLAP MY HANDS AND 94 00:03:20,880 --> 00:03:23,520 NOW WE SHOULD GO AHEAD TO THE 95 00:03:23,520 --> 00:03:30,400 SECOND TALK, WHICH IS ENTITLED 96 00:03:30,400 --> 00:03:33,000 ANCYTOKINE AUTO ANTIBODIES: 97 00:03:33,000 --> 00:03:33,960 IMPORTANT UNDERAPPRECIATED 98 00:03:33,960 --> 00:03:35,240 COFACTORS IN RARE AND COMMON 99 00:03:35,240 --> 00:03:36,080 CONDITIONS. 100 00:03:36,080 --> 00:03:42,560 THE SPEAKER WILL BE THE 101 00:03:42,560 --> 00:03:44,720 INCOMPARABLE DR. STEVEN HOLLAND, 102 00:03:44,720 --> 00:03:48,080 NIH DISTINGUISHED INVESTIGATOR, 103 00:03:48,080 --> 00:03:49,640 HE HAS A LAB THERE IN THE NIAID 104 00:03:49,640 --> 00:03:51,440 AS WELL. 105 00:03:51,440 --> 00:03:55,800 HE'S THE EMERITUS DEPUTY DIRECT 106 00:03:55,800 --> 00:03:57,360 DIRECTOR FOR INTRAMURAL CLINICAL 107 00:03:57,360 --> 00:03:58,920 RESEARCH, GOT HIS MEDICAL DEGREE 108 00:03:58,920 --> 00:04:00,400 IN INFECTIOUS DISEASES 109 00:04:00,400 --> 00:04:01,760 FELLOWSHIP AT JOHNS HOPKINS AND 110 00:04:01,760 --> 00:04:04,240 HE'S A MEMBER OF THE NATIONAL 111 00:04:04,240 --> 00:04:04,920 ACADEMY OF MEDICINE. 112 00:04:04,920 --> 00:04:06,960 HIS RESEARCH INTEREST IS IN THE 113 00:04:06,960 --> 00:04:08,720 GENETIC SUSCEPTIBILITY TO 114 00:04:08,720 --> 00:04:09,600 PRIMARY IMMUNODEFICIENCY 115 00:04:09,600 --> 00:04:12,080 DISEASE, MECHANISMS OF BACTERIAL 116 00:04:12,080 --> 00:04:13,720 PATHOGENESIS, AND CYTOKINES AND 117 00:04:13,720 --> 00:04:15,640 THEIR RECEPTORS IN THE 118 00:04:15,640 --> 00:04:19,040 PATHOGENESIS AND THERAPY OF 119 00:04:19,040 --> 00:04:20,760 INFECTIONS. 120 00:04:20,760 --> 00:04:21,920 WELL, WITHOUT FURTHER ADO, WE 121 00:04:21,920 --> 00:04:23,840 NEED TO GET ON TO IT BECAUSE WE 122 00:04:23,840 --> 00:04:26,600 HAVE A SPK SPECTACULAR SESSION IN 123 00:04:26,600 --> 00:04:27,880 STORE FOR US, AND I WOULD JUST 124 00:04:27,880 --> 00:04:30,120 LIKE TO HAVE DR. CRISWELL TAKE 125 00:04:30,120 --> 00:04:32,680 IT AWAY! 126 00:04:32,680 --> 00:04:34,640 SO THANK YOU SO MUCH, DAN, FOR 127 00:04:34,640 --> 00:04:39,000 THAT INTRODUCTION, AND MY THANKS 128 00:04:39,000 --> 00:04:40,280 TO WIN TO PRESENT PART OF THIS 129 00:04:40,280 --> 00:04:40,480 SERIES. 130 00:04:40,480 --> 00:04:41,920 IT'S A GREAT HONOR AND 131 00:04:41,920 --> 00:04:42,200 PRIVILEGE. 132 00:04:42,200 --> 00:04:43,840 AND I HAVE NO DISCLOSURES TO 133 00:04:43,840 --> 00:04:46,920 REPORT. 134 00:04:46,920 --> 00:04:48,280 SO I'M GOING TO BEGIN WITH A 135 00:04:48,280 --> 00:04:50,000 VERY BRIEF OVERVIEW OF LUPUS. 136 00:04:50,000 --> 00:04:52,280 AS WE HEARD, WE HAVE A WONDERFUL 137 00:04:52,280 --> 00:04:53,600 OPPORTUNITY TO INTERVIEW A 138 00:04:53,600 --> 00:04:55,840 WOMAN, JENNIFER, WHO HAS 139 00:04:55,840 --> 00:04:57,200 EXPERIENCED LIFE WITH LUPUS FOR 140 00:04:57,200 --> 00:04:58,800 MANY, MANY YEARS. 141 00:04:58,800 --> 00:05:02,600 I FIRST MET JENNIFER WHEN SHE 142 00:05:02,600 --> 00:05:03,560 VOLUNTEERED FOR ONE OF MY 143 00:05:03,560 --> 00:05:05,120 RESEARCH PROJECTS AND I KNOW 144 00:05:05,120 --> 00:05:06,880 YOU'LL REALLY ENJOY HEARING HER 145 00:05:06,880 --> 00:05:08,280 STORY. 146 00:05:08,280 --> 00:05:09,120 AFTER THE INTERVIEW WITH 147 00:05:09,120 --> 00:05:09,880 JENNIFER, I'LL SHARE WITH YOU 148 00:05:09,880 --> 00:05:11,840 SOME OF THE PROGRESS RELATED TO 149 00:05:11,840 --> 00:05:12,840 DEFINING THE GENETIC 150 00:05:12,840 --> 00:05:14,000 CONTRIBUTION TO THE DISEASE, 151 00:05:14,000 --> 00:05:15,640 INCLUDING HOW IT'S HELPED US 152 00:05:15,640 --> 00:05:17,480 UNDERSTAND ETIOLOGIC PATHWAYS 153 00:05:17,480 --> 00:05:19,080 THAT OPERATE IN LUPUS, AND THEN 154 00:05:19,080 --> 00:05:20,920 I'LL SHARE WITH YOU WHAT WE'RE 155 00:05:20,920 --> 00:05:22,560 LEARNING ABOUT THE EPIGENETIC 156 00:05:22,560 --> 00:05:25,400 CONTRIBUTION TO THE DISEASE. 157 00:05:25,400 --> 00:05:27,760 I'LL FOCUS ON STUDIES INVOLVING 158 00:05:27,760 --> 00:05:28,680 THE EPIGENETIC MODIFICATION OF 159 00:05:28,680 --> 00:05:31,960 DNA METHYLATION, IN PART BECAUSE 160 00:05:31,960 --> 00:05:35,320 OF THE IMPORTANT LINK TO THE 161 00:05:35,320 --> 00:05:38,760 ENVIRONMENT. 162 00:05:38,760 --> 00:05:43,000 SO LUPUS IS THE PROAT TYPIC 163 00:05:43,000 --> 00:05:45,240 SYSTEMIC AUTOIMMUNE DISEASE. 164 00:05:45,240 --> 00:05:46,800 LIKE MANY AUTOIMMUNE DISEASES, 165 00:05:46,800 --> 00:05:50,280 WOMEN ARE AT DRAMATICALLY 166 00:05:50,280 --> 00:05:51,240 INCREASED RISK COMPARED TO MEN 167 00:05:51,240 --> 00:05:54,320 WITH A TENFOLD INCREASE. 168 00:05:54,320 --> 00:05:56,760 ETHNIC MINORITIES ARE ALSO AT 169 00:05:56,760 --> 00:05:59,400 INCREASE FOR DISEASE, A REALLY 170 00:05:59,400 --> 00:06:00,000 STRIKING FEATURE. 171 00:06:00,000 --> 00:06:01,520 THE DISEASE IS ASSOCIATED WITH 172 00:06:01,520 --> 00:06:03,840 VERY SUBSTANTIAL MORBIDITY AND 173 00:06:03,840 --> 00:06:05,080 MORTALITY. 174 00:06:05,080 --> 00:06:07,200 THE ETIOLOGY IS COMPLEX, BUT 175 00:06:07,200 --> 00:06:10,480 THERE IS A CLEAR-CUT GENETIC 176 00:06:10,480 --> 00:06:10,800 CONTRIBUTION. 177 00:06:10,800 --> 00:06:15,560 AND THERE IS NO PATH PNEUMONIC 178 00:06:15,560 --> 00:06:16,160 TEST FOR DIAGNOSIS, WHICH HAS 179 00:06:16,160 --> 00:06:17,800 BEEN A MAJOR CHALLENGE, NOT ONLY 180 00:06:17,800 --> 00:06:19,160 FOR DIAGNOSIS BUT ALSO FOR 181 00:06:19,160 --> 00:06:20,800 TRYING TO UNDERSTAND THE 182 00:06:20,800 --> 00:06:23,520 ETIOLOGIC CONTRIBUTION TO THE 183 00:06:23,520 --> 00:06:23,840 DISEASE. 184 00:06:23,840 --> 00:06:27,720 IT'S A CHRONIC ILLNESS WITH NO 185 00:06:27,720 --> 00:06:30,600 CURE. 186 00:06:30,600 --> 00:06:36,280 ALTHOUGH THERE HAS BEEN RECENT 187 00:06:36,280 --> 00:06:37,200 PROGRESS IN THIS DISEASE. 188 00:06:37,200 --> 00:06:39,520 SO THIS SLIDE JUST ILLUSTRATES 189 00:06:39,520 --> 00:06:40,840 SOME OF THE MANY MANIFESTATIONS 190 00:06:40,840 --> 00:06:48,000 OF THE DISEASE. 191 00:06:48,000 --> 00:06:49,320 ESPECIALLY PROMINENT ARE A 192 00:06:49,320 --> 00:06:51,200 VARIETY OF SKIN MANIFESTATIONS 193 00:06:51,200 --> 00:06:51,480 IN LUPUS. 194 00:06:51,480 --> 00:06:54,240 SHOWN HERE IS THE CLASSIC 195 00:06:54,240 --> 00:06:56,640 BUTTERFLY RASH, DISCOID RASH 196 00:06:56,640 --> 00:06:58,600 WHICH CAN BE QUITE DISFIGURING, 197 00:06:58,600 --> 00:06:59,680 PHOTOSENSITIVITY CAN BE 198 00:06:59,680 --> 00:07:01,680 OBSERVED, CAN BE VERY PROMINENT. 199 00:07:01,680 --> 00:07:03,960 KIDNEY INVOLVEMENT IS ONE OF THE 200 00:07:03,960 --> 00:07:05,160 MOST SERIOUS COMPLICATIONS OF 201 00:07:05,160 --> 00:07:07,400 THE DISEASE. 202 00:07:07,400 --> 00:07:09,440 AND CAN LEAD TO END STAGE RENAL 203 00:07:09,440 --> 00:07:10,440 FAILURE, EVEN DEATH. 204 00:07:10,440 --> 00:07:12,040 INVOLVEMENT OF THE CENTRAL 205 00:07:12,040 --> 00:07:12,960 NERVOUS SYSTEM IS RELATIVELY 206 00:07:12,960 --> 00:07:13,560 COMMON. 207 00:07:13,560 --> 00:07:14,800 ARTHRITIS IS ALSO COME, BUT 208 00:07:14,800 --> 00:07:16,240 THERE ARE MANY MORE 209 00:07:16,240 --> 00:07:17,160 MANIFESTATIONS NOT PICTURED ON 210 00:07:17,160 --> 00:07:22,680 THE SLIDE. 211 00:07:22,680 --> 00:07:24,200 LUPUS IS ALSO STRIKING FOR THE 212 00:07:24,200 --> 00:07:25,680 NUMEROUS AUTO ANTIBODIES THAT 213 00:07:25,680 --> 00:07:26,400 ARE PRESENT AMONG INDIVIDUALS 214 00:07:26,400 --> 00:07:29,400 WITH THE DISEASE. 215 00:07:29,400 --> 00:07:31,280 MANY OF WHICH HAVE VERY SPECIFIC 216 00:07:31,280 --> 00:07:32,160 CLINICAL ASSOCIATIONS. 217 00:07:32,160 --> 00:07:38,680 THESE INCLUDE THROMBOSIS, 218 00:07:38,680 --> 00:07:41,640 ANTISSA AND SSB SKIN 219 00:07:41,640 --> 00:07:43,680 MANIFESTATIONS WITH NEONATAL 220 00:07:43,680 --> 00:07:45,160 HEART BLOCK, ANTIDOUBLE STRANDED 221 00:07:45,160 --> 00:07:46,360 DNA ANTIBODIES ARE ASSOCIATED 222 00:07:46,360 --> 00:07:47,600 WITH RENAL DISEASE. 223 00:07:47,600 --> 00:07:49,320 THERE'S ALSO INCREASING EVIDENCE 224 00:07:49,320 --> 00:07:51,880 THAT THE ANTIBODIES MAY HAVE THE 225 00:07:51,880 --> 00:07:52,920 STRONGEST ASSOCIATIONS WITH 226 00:07:52,920 --> 00:07:58,720 SPECIFIC GENETIC FACTORS. 227 00:07:58,720 --> 00:08:00,640 SO NOW LET ME TURN TO JENNIFER'S 228 00:08:00,640 --> 00:08:00,840 STORY. 229 00:08:00,840 --> 00:08:02,560 I'M GOING TO TOUCH UPON HER 230 00:08:02,560 --> 00:08:03,560 EXPERIENCE GETTING DIAGNOSED 231 00:08:03,560 --> 00:08:10,200 WITH LUPUS, WHAT IT MEANT IF SHE 232 00:08:10,200 --> 00:08:10,840 CONTEMPLATED HAVING CHILDREN. 233 00:08:10,840 --> 00:08:12,600 THE MANY CHALLENGES SHE 234 00:08:12,600 --> 00:08:15,680 EXPERIENCED LIVING WITH LUPUS, 235 00:08:15,680 --> 00:08:17,720 WHAT IT WAS LIKE TO BE A LUPUS 236 00:08:17,720 --> 00:08:20,880 PATIENT IN THE ERA OF COVID, AND 237 00:08:20,880 --> 00:08:22,440 LASTLY, THE ROLE OF RESEARCH, 238 00:08:22,440 --> 00:08:24,280 WHAT THAT'S MEANT TO HER, OVER 239 00:08:24,280 --> 00:08:30,280 THE PAST COUPLE OF DECADES. 240 00:08:30,280 --> 00:08:31,600 THANK YOU SO MUCH FOR JOINING 241 00:08:31,600 --> 00:08:31,920 US. 242 00:08:31,920 --> 00:08:33,640 I KNOW THE AUDIENCE IS GOING TO 243 00:08:33,640 --> 00:08:34,800 REALLY APPRECIATE HEARING YOUR 244 00:08:34,800 --> 00:08:35,200 STORY. 245 00:08:35,200 --> 00:08:36,840 SO WHY DON'T YOU BEGIN BY 246 00:08:36,840 --> 00:08:38,040 TELLING US YOUR EXPERIENCE 247 00:08:38,040 --> 00:08:39,760 GETTING DIAGNOSED, WHAT YOUR 248 00:08:39,760 --> 00:08:42,160 FIRST FEW SYMPTOMS WERE, WHAT 249 00:08:42,160 --> 00:08:45,360 LED TO THE DIAGNOSIS AND WHAT 250 00:08:45,360 --> 00:08:48,520 YOU WERE EXPERIENCING AT THAT 251 00:08:48,520 --> 00:08:49,640 TIME. 252 00:08:49,640 --> 00:08:50,520 >> FIRST THANK YOU FOR HAVING 253 00:08:50,520 --> 00:08:51,000 ME. 254 00:08:51,000 --> 00:08:52,240 I'M HONORED TO BE ABLE TO SHARE 255 00:08:52,240 --> 00:08:52,720 MY STORY TODAY. 256 00:08:52,720 --> 00:08:57,840 IN TERMS OF DIAGNOSIS, I WAS 257 00:08:57,840 --> 00:08:58,840 DIAGNOSED JUST OVER 30 YEARS 258 00:08:58,840 --> 00:09:00,240 AGO, SO I'VE LIVED MORE THAN 259 00:09:00,240 --> 00:09:05,440 HALF OF MY LIFE WITH LUPUS. 260 00:09:05,440 --> 00:09:07,000 I JUST FINISHED MY SECOND YEAR 261 00:09:07,000 --> 00:09:08,200 OF UNDERGRADUATE STUDIES AT THE 262 00:09:08,200 --> 00:09:09,680 TIME, AND REALLY IT WAS AROUND 263 00:09:09,680 --> 00:09:13,240 MAY OF THAT YEAR, TWO THINGS 264 00:09:13,240 --> 00:09:14,280 HAPPENED SIMULTANEOUSLY. 265 00:09:14,280 --> 00:09:15,640 THE FIRST THING WAS I DEVELOPED 266 00:09:15,640 --> 00:09:19,200 A VERY ROBUST COUGH, AND PAIN IN 267 00:09:19,200 --> 00:09:21,280 THE CHEST WITH DEEP BREATHS. 268 00:09:21,280 --> 00:09:23,040 AND THAT WAS DIAGNOSED FAIRLY 269 00:09:23,040 --> 00:09:25,280 QUICKLY BY MY PRIMARY CARE 270 00:09:25,280 --> 00:09:26,440 PROVIDER AS WHOOPING COUGH. 271 00:09:26,440 --> 00:09:28,280 SO I WAS GIVEN TYLENOL WITH 272 00:09:28,280 --> 00:09:30,600 CODEINE TO HELP ME SLEEP. 273 00:09:30,600 --> 00:09:34,160 AND THAT WAS THAT. 274 00:09:34,160 --> 00:09:35,760 SIMULTANEOUSLY, I HAVE A ROUTINE 275 00:09:35,760 --> 00:09:36,640 PHYSICAL AND THE LAB RESULTS 276 00:09:36,640 --> 00:09:42,680 FROM THAT PHYSICAL KEPT COMING 277 00:09:42,680 --> 00:09:45,160 BACK AB NOR MA'AM, SO I'D GO 278 00:09:45,160 --> 00:09:46,560 BACK AND GIVE MORE BLOOD AND 279 00:09:46,560 --> 00:09:48,640 THEY'D RUN MORE TESTS. 280 00:09:48,640 --> 00:09:49,640 OVER THE COURSE OF SEVERAL 281 00:09:49,640 --> 00:09:51,240 MONTHS I HEARD INITIALLY FALSE 282 00:09:51,240 --> 00:09:52,400 POSITIVE FOR SYPHILIS, WHICH I 283 00:09:52,400 --> 00:09:54,000 KNEW WAS NOT THE CASE. 284 00:09:54,000 --> 00:09:57,920 THEN I HEARD A CONNECTIVE TISSUE 285 00:09:57,920 --> 00:09:58,840 DISORDER POTENTIALLY. 286 00:09:58,840 --> 00:10:00,360 I RECALL HEARING POTENTIALLY A 287 00:10:00,360 --> 00:10:01,600 BLOOD CANCER. 288 00:10:01,600 --> 00:10:05,360 SO THIS SERIES OF DISTURBING 289 00:10:05,360 --> 00:10:08,400 RESULTS SORT OF PARALLELLED THE 290 00:10:08,400 --> 00:10:10,680 TRACK OF THE REALLY PERSISTENT 291 00:10:10,680 --> 00:10:11,880 AND UNCOMFORTABLE COUGH. 292 00:10:11,880 --> 00:10:13,440 AFTER ABOUT THREE MONTHS OF 293 00:10:13,440 --> 00:10:15,440 THIS, I RECEIVED A CALL FROM A 294 00:10:15,440 --> 00:10:17,160 NURSE IN THE PRIMARY CARE OFFICE 295 00:10:17,160 --> 00:10:20,240 WHO SAID THE DOCTOR HAD READ AN 296 00:10:20,240 --> 00:10:22,400 ARTICLE, AND THE DOCTOR 297 00:10:22,400 --> 00:10:23,360 SUSPECTED THAT THE WHOOPING 298 00:10:23,360 --> 00:10:26,360 COUGH WAS ACTUALLY PLUR SEE, AND 299 00:10:26,360 --> 00:10:30,640 THAT THE ABNORMAL LABS WERE DUE 300 00:10:30,640 --> 00:10:31,280 TO ANTIPHOSPHOLIPID ANTIBODIES. 301 00:10:31,280 --> 00:10:32,840 AND SHE TOLD ME THREE THINGS 302 00:10:32,840 --> 00:10:34,680 THAT DAY. 303 00:10:34,680 --> 00:10:36,760 IT WAS THE DAY BEFORE MY 20TH 304 00:10:36,760 --> 00:10:38,600 BIRTHDAY, THAT I LIKELY HAD 305 00:10:38,600 --> 00:10:42,080 SYSTEMIC LUPUS, THAT I WAS AT 306 00:10:42,080 --> 00:10:43,960 VERY HIGH RISK FOR A STROKE, AND 307 00:10:43,960 --> 00:10:45,800 THAT IT WAS UNLIKELY I WOULD 308 00:10:45,800 --> 00:10:47,760 EVER BE ABLE TO CARRY A 309 00:10:47,760 --> 00:10:49,000 PREGNANCY BECAUSE OF THE 310 00:10:49,000 --> 00:10:52,040 CLOTTING RISK. 311 00:10:52,040 --> 00:10:53,040 MY PARENTS PAID OUT OF POCKET 312 00:10:53,040 --> 00:10:54,520 FOR ME TO SEE A RHEUMATOLOGIST 313 00:10:54,520 --> 00:11:00,760 SO I WOULDN'T HAVE -- 314 00:11:00,760 --> 00:11:07,680 IMMEDIATELY THAT I HAD LUPUS. 315 00:11:07,680 --> 00:11:08,840 AND WHEN I ASKED WHAT WAS GOING 316 00:11:08,840 --> 00:11:10,600 TO HAPPEN TO ME, I WAS TOLD, 317 00:11:10,600 --> 00:11:15,480 "WE'LL KNOW IN A YEAR." 318 00:11:15,480 --> 00:11:17,120 >> SO WHAT A DEVASTATING BLOW AT 319 00:11:17,120 --> 00:11:18,040 THE AGE OF 20, YOU'RE IN 320 00:11:18,040 --> 00:11:18,600 COLLEGE. 321 00:11:18,600 --> 00:11:19,320 I CAN ONLY IMAGINE WHAT WAS 322 00:11:19,320 --> 00:11:21,720 GOING THROUGH YOUR HEAD. 323 00:11:21,720 --> 00:11:23,520 SO I KNOW THAT YOU WENT ON TO 324 00:11:23,520 --> 00:11:26,000 HAVE SOME OTHER MANIFESTATIONS 325 00:11:26,000 --> 00:11:27,240 THAT YOU STRUGGLED TO KIND OF 326 00:11:27,240 --> 00:11:29,160 FIND THE RIGHT TREATMENT AND 327 00:11:29,160 --> 00:11:31,240 BALANCING THAT WITH SIDE EFFECTS 328 00:11:31,240 --> 00:11:32,760 AND I THINK THE AUDIENCE WOULD 329 00:11:32,760 --> 00:11:35,280 ALSO BE INTERESTED IN HEARING 330 00:11:35,280 --> 00:11:38,040 MORE ABOUT HOW YOU PURSUED YOUR 331 00:11:38,040 --> 00:11:41,680 DESIRE TO HAVE CHILDREN. 332 00:11:41,680 --> 00:11:44,120 AND HOW YOU GOT TO THE POINT 333 00:11:44,120 --> 00:11:45,240 WHERE THAT BECAME A POSSIBILITY 334 00:11:45,240 --> 00:11:46,280 AND THEN YOUR EXPERIENCE WITH 335 00:11:46,280 --> 00:11:47,640 YOUR PREGNANCY. 336 00:11:47,640 --> 00:11:49,400 >> YES. 337 00:11:49,400 --> 00:11:50,920 WELL, DURING THAT YEAR, IT 338 00:11:50,920 --> 00:11:53,360 BECAME CLEAR THAT I WAS GOING TO 339 00:11:53,360 --> 00:11:57,240 HAVE PRIMARILY ARTHRITIS IN 340 00:11:57,240 --> 00:11:58,960 MULTIPLE JOINTS, INFLAMMATORY 341 00:11:58,960 --> 00:12:00,680 ARTHRITIS BECAME MY MAIN 342 00:12:00,680 --> 00:12:02,320 CHALLENGE. 343 00:12:02,320 --> 00:12:04,440 ALSO PHOTOSENSITIVITY, RASHES IN 344 00:12:04,440 --> 00:12:07,400 THE SUN. 345 00:12:07,400 --> 00:12:11,080 I DEVELOPED A FULL MYLAR RASH 346 00:12:11,080 --> 00:12:14,040 WHILE PREGNANT, SO I'VE HAD SOME 347 00:12:14,040 --> 00:12:14,560 SKIN COMPONENTS. 348 00:12:14,560 --> 00:12:18,200 I WILL SAY THAT BEING TOLD I 349 00:12:18,200 --> 00:12:19,760 COULDN'T HAVE CHILDREN WAS NOT 350 00:12:19,760 --> 00:12:22,200 SOMETHING I WAS WILLING TO 351 00:12:22,200 --> 00:12:22,440 ACCEPT. 352 00:12:22,440 --> 00:12:24,360 AND I HAVE TO SAY THAT BECAUSE I 353 00:12:24,360 --> 00:12:25,800 WAS INVOLVED AS A RESEARCH 354 00:12:25,800 --> 00:12:28,520 SUBJECT IN YOUR RESEARCH 355 00:12:28,520 --> 00:12:30,840 PROJECTS, I THINK I HAD SO MUCH 356 00:12:30,840 --> 00:12:34,200 FAITH IN RESEARCH AND POTENTIAL 357 00:12:34,200 --> 00:12:35,760 ADVANCEMENT IN OUR UNDERSTANDING 358 00:12:35,760 --> 00:12:38,680 OF THIS DISEASE THAT I REALLY 359 00:12:38,680 --> 00:12:42,320 PUSHED AND WAS FINALLY CONNECTED 360 00:12:42,320 --> 00:12:44,000 WITH A HIGH RISK O.B. WHO WAS 361 00:12:44,000 --> 00:12:45,440 WILLING TO TAKE ON MY CASE, AND 362 00:12:45,440 --> 00:12:48,080 I FOUND A TEACHING HOSPITAL, I 363 00:12:48,080 --> 00:12:49,040 WANTED DELIBERATELY TO GIVE 364 00:12:49,040 --> 00:12:50,600 BIRTH IF I COULD GET PREGNANT AT 365 00:12:50,600 --> 00:12:53,600 A TEACHING HOSPITAL BECAUSE I 366 00:12:53,600 --> 00:12:57,280 BELIEVED I COULD GET THE LATEST, 367 00:12:57,280 --> 00:12:59,240 MOST ATTENTIVE CARE THERE. 368 00:12:59,240 --> 00:13:01,440 SO IN 2000, IN MY VERY LATE 369 00:13:01,440 --> 00:13:04,440 20s, WHEN I FINALLY WAS READY 370 00:13:04,440 --> 00:13:06,160 TO HAVE CHILDREN, THE PLAN WAS I 371 00:13:06,160 --> 00:13:07,880 WOULD GIVE MYSELF TWICE DAILY 372 00:13:07,880 --> 00:13:13,320 INJECTIONS OF LOVENOX TO SORT OF 373 00:13:13,320 --> 00:13:13,880 PROPHYLACTICALLY PREVENT ANY 374 00:13:13,880 --> 00:13:17,760 KIND OF CLOTTING, AND OTHER RISK 375 00:13:17,760 --> 00:13:19,800 FACTORS I KNEW OF, I HAD 376 00:13:19,800 --> 00:13:22,960 ANTIBODIES THAT PUT THE -- WOULD 377 00:13:22,960 --> 00:13:25,920 PUT THE BABY AT RISK FOR FETAL 378 00:13:25,920 --> 00:13:27,240 HEART BLOCK, SO THEY WERE 379 00:13:27,240 --> 00:13:29,000 MONITORING FOR THAT, OBVIOUSLY 380 00:13:29,000 --> 00:13:29,960 HOPEFULLY TRYING TO KEEP MY 381 00:13:29,960 --> 00:13:30,960 LUPUS UNDER CONTROL. 382 00:13:30,960 --> 00:13:32,880 THE WILDCARD WAS WHEN I DID GET 383 00:13:32,880 --> 00:13:34,800 PREGNANT, IT WAS A SPONTANEOUS 384 00:13:34,800 --> 00:13:36,920 TWIN PREGNANCY, SO THEN 385 00:13:36,920 --> 00:13:39,640 MULTIPLES CAME INTO PLAY. 386 00:13:39,640 --> 00:13:40,840 I WAS FINE, REALLY, UNTIL THE 387 00:13:40,840 --> 00:13:43,400 END OF MY 33RD WEEK, AND I 388 00:13:43,400 --> 00:13:45,680 DEVELOPED SUDDENLY VERY HIGH 389 00:13:45,680 --> 00:13:46,880 BLOOD PRESSURE, AND NOTICEABLE 390 00:13:46,880 --> 00:13:49,640 SWELLING. 391 00:13:49,640 --> 00:13:51,480 I WAS ADMITTED TO THE HOSPITAL 392 00:13:51,480 --> 00:13:54,320 AND THE HIGH RISK O.B., I 393 00:13:54,320 --> 00:13:57,040 REMEMBER HIM, MY DOCTOR WAS OUT 394 00:13:57,040 --> 00:13:59,040 OF TOWN, HIS PARTNER WAS THERE, 395 00:13:59,040 --> 00:14:01,400 AND HE SAID, WHERE ARE YOUR 396 00:14:01,400 --> 00:14:01,960 LIVER LABS? 397 00:14:01,960 --> 00:14:03,600 HE KEPT ASKING ME OVER AND OVER 398 00:14:03,600 --> 00:14:03,840 AGAIN. 399 00:14:03,840 --> 00:14:05,720 THERE WEREN'T ANY LIVER LABS. 400 00:14:05,720 --> 00:14:10,080 BUT HE SUSPECTED AND CONFIRMED I 401 00:14:10,080 --> 00:14:10,840 HAD HELP SYNDROME. 402 00:14:10,840 --> 00:14:13,720 SO THEY DELIVERED THE BABIES BY 403 00:14:13,720 --> 00:14:17,440 EMERGENCY C-SECTION AT EXACTLY 404 00:14:17,440 --> 00:14:18,640 34 WEEKS. 405 00:14:18,640 --> 00:14:20,160 ONE WAS 3 POUNDS 12 OUNCES, THE 406 00:14:20,160 --> 00:14:22,840 OTHER WAS 5 POUNDS ROUGHLY. 407 00:14:22,840 --> 00:14:24,920 I REMAINED HOSPITALIZED FOR A 408 00:14:24,920 --> 00:14:27,440 WEEK, DEVELOPED CLOTS IN THE 409 00:14:27,440 --> 00:14:28,760 C-SECTION THAT WAS LEFT OPEN AND 410 00:14:28,760 --> 00:14:30,200 PACKED DAILY FOR ABOUT SIX WEEKS 411 00:14:30,200 --> 00:14:31,840 TO HEAL. 412 00:14:31,840 --> 00:14:33,440 VERY PAINFUL. 413 00:14:33,440 --> 00:14:35,720 THE BABIES WERE IN THE NICU FOR 414 00:14:35,720 --> 00:14:39,800 ABOUT TWO WEEKS, BUT WE ALL 415 00:14:39,800 --> 00:14:40,800 SURVIVED. 416 00:14:40,800 --> 00:14:41,960 >> REMARKABLE. 417 00:14:41,960 --> 00:14:43,080 AND THAT WAS THE HELP SYNDROME 418 00:14:43,080 --> 00:14:45,000 WHICH IS A FORM OF SEVERE 419 00:14:45,000 --> 00:14:46,840 PREECLAMPSIA FOR THE AUDIENCE, 420 00:14:46,840 --> 00:14:52,800 VERY SCARY PERIOD. 421 00:14:52,800 --> 00:14:54,000 SO SO MAYBE YOU CAN SHARE A 422 00:14:54,000 --> 00:14:56,000 LITTLE ABOUT LUPUS AS A CHRONIC 423 00:14:56,000 --> 00:14:56,240 ILLNESS. 424 00:14:56,240 --> 00:14:57,800 YOU ENDED UP HAVING TO CHANGE 425 00:14:57,800 --> 00:14:59,480 HEALTH INSURANCE PLANS OVER TIME 426 00:14:59,480 --> 00:15:00,960 AND HOW YOU STRUGGLED WITH 427 00:15:00,960 --> 00:15:03,640 CONTINUITY OF CARE AND THEN 428 00:15:03,640 --> 00:15:05,640 MAYBE YOU COULD TALK ABOUT THE 429 00:15:05,640 --> 00:15:10,840 NEW MEDICATION THAT WAS ADDED, 430 00:15:10,840 --> 00:15:11,760 VANLISTA, AND WHAT THAT MEANT 431 00:15:11,760 --> 00:15:14,240 WHEN WE ENTERED THE ERA OF THE 432 00:15:14,240 --> 00:15:14,680 PANDEMIC. 433 00:15:14,680 --> 00:15:15,240 >> YES. 434 00:15:15,240 --> 00:15:22,880 WELL, LOOKING BACK OVER 30 435 00:15:22,880 --> 00:15:25,040 YEARS, TWO THEMES HAVE BEEN 436 00:15:25,040 --> 00:15:26,000 FAIRLY CONSISTENT CONSISTENT 437 00:15:26,000 --> 00:15:27,480 WITH THE WORKLOAD OF MANAGING 438 00:15:27,480 --> 00:15:27,800 LUPUS. 439 00:15:27,800 --> 00:15:29,200 IT'S A SIGNIFICANT AMOUNT OF 440 00:15:29,200 --> 00:15:30,720 WORK TO MANAGE A CHRONIC 441 00:15:30,720 --> 00:15:32,000 ILLNESS, AND IN PARTICULAR, ONE 442 00:15:32,000 --> 00:15:33,320 WHICH NOT ALL DOCTORS ARE VERY 443 00:15:33,320 --> 00:15:36,760 WELL VERSED, THAT PUTS A LOT OF 444 00:15:36,760 --> 00:15:38,320 RESPONSIBILITY BACK ON THE 445 00:15:38,320 --> 00:15:39,760 PATIENT. 446 00:15:39,760 --> 00:15:41,440 CERTAINLY CHALLENGES, CARE 447 00:15:41,440 --> 00:15:42,600 CONTINUITY, ANY LIFE CHANGE IN 448 00:15:42,600 --> 00:15:43,320 THE UNITED STATES, BECAUSE WE 449 00:15:43,320 --> 00:15:48,320 HAVE A FRAGMENTED HEALTH SYSTEM, 450 00:15:48,320 --> 00:15:49,320 OFTEN NECESSITATES A CHANGE IN 451 00:15:49,320 --> 00:15:50,200 INSURANCE AND A CHANGE IN 452 00:15:50,200 --> 00:15:51,680 PROVIDERS. 453 00:15:51,680 --> 00:15:53,160 AND EVEN IF ALL YOUR PROVIDERS 454 00:15:53,160 --> 00:15:56,240 USE THE SAME ELECTRONIC HEALTH 455 00:15:56,240 --> 00:15:57,480 RECORD, IT DOESN'T ENSURE 456 00:15:57,480 --> 00:16:02,480 CONTINUITY OF TREND LINES. 457 00:16:02,480 --> 00:16:04,400 EVEN THOUGH THEY'RE AVAILABLE, 458 00:16:04,400 --> 00:16:05,440 APPOINTMENTS ARE SHORT AND IT'S 459 00:16:05,440 --> 00:16:08,680 NOT READILY AVAILABLE TO 460 00:16:08,680 --> 00:16:08,960 PROVIDERS. 461 00:16:08,960 --> 00:16:10,800 SO I FIND A LOT OF 462 00:16:10,800 --> 00:16:11,720 RESPONSIBILITY FOR CARE 463 00:16:11,720 --> 00:16:15,560 CONTINUITY FALLS ON THE PATIENT. 464 00:16:15,560 --> 00:16:17,520 SOMETIMES I MISS THE DAYS OF 465 00:16:17,520 --> 00:16:18,640 HAND-CARRYING RECORDS BETWEEN 466 00:16:18,640 --> 00:16:20,440 PROVIDERS, BECAUSE THAT WAS A 467 00:16:20,440 --> 00:16:22,520 LITTLE MORE -- SEEMED MORE 468 00:16:22,520 --> 00:16:25,680 RELIABLE OFTENTIMES. 469 00:16:25,680 --> 00:16:29,840 THE OTHER THING THAT HAS BEEN A 470 00:16:29,840 --> 00:16:31,040 REAL -- MEDICATIONS FOR LUPUS, 471 00:16:31,040 --> 00:16:33,080 IN TERMS OF, A, WE HAVEN'T HAD A 472 00:16:33,080 --> 00:16:35,800 LOT OF NEW MEDICATIONS UNTIL 473 00:16:35,800 --> 00:16:39,720 FAIRLY RECENTLY. 474 00:16:39,720 --> 00:16:41,040 AND IT'S NOT UNUSUAL TO HAVE 475 00:16:41,040 --> 00:16:42,080 MEDICATIONS THAT HAVE SIDE 476 00:16:42,080 --> 00:16:43,080 EFFECTS THAT DON'T WORK FOR YOU, 477 00:16:43,080 --> 00:16:44,840 SO YOU HAVE TO DISCONTINUE 478 00:16:44,840 --> 00:16:46,040 THOSE, OR MEDICATIONS THAT MAYBE 479 00:16:46,040 --> 00:16:47,840 WORK WELL FOR YOU BUT GET PULLED 480 00:16:47,840 --> 00:16:49,840 OFF THE MARKET OR GET A BLACK 481 00:16:49,840 --> 00:16:51,560 BOX WARNING BECAUSE SUDDENLY 482 00:16:51,560 --> 00:16:52,920 THEY'RE KNOWN TO CAUSE CLOTTING 483 00:16:52,920 --> 00:16:54,800 RISK. 484 00:16:54,800 --> 00:16:57,400 SOME MEDS ARE NOT ADVISED TO BE 485 00:16:57,400 --> 00:17:02,480 TAKEN LONG TERM LIKE PREDNISONE. 486 00:17:02,480 --> 00:17:03,760 I'M VERY FORTUNATE IN THAT I WAS 487 00:17:03,760 --> 00:17:08,840 ABLE TO START TAKING BENLISTA 488 00:17:08,840 --> 00:17:11,240 INFUSIONS, I THINK THAT'S A 489 00:17:11,240 --> 00:17:11,880 MONOCLONAL ANTIBODY. 490 00:17:11,880 --> 00:17:13,520 I STARTED THAT IN 2019. 491 00:17:13,520 --> 00:17:15,240 BUT AGAIN, GOING BACK TO THE 492 00:17:15,240 --> 00:17:19,320 WORK, IT TAKES TIME OUT OF YOUR 493 00:17:19,320 --> 00:17:20,640 DAY TO GO GET AN INFUSION, SIT 494 00:17:20,640 --> 00:17:22,360 THERE FOR A COUPLE HOURS, AND 495 00:17:22,360 --> 00:17:26,040 ALSO THE MEDICATIONS ARE VERY 496 00:17:26,040 --> 00:17:27,240 EXPENSIVE, AND THAT PUTS A LOT 497 00:17:27,240 --> 00:17:29,160 OF WORK THEN ON THE PATIENT TO 498 00:17:29,160 --> 00:17:30,320 TRY TO FIGURE OUT HOW TO PAY FOR 499 00:17:30,320 --> 00:17:34,040 IT, HOW TO ACCESS PATIENT 500 00:17:34,040 --> 00:17:39,120 ASSISTANCE PROGRAMS AND TO WEIGH 501 00:17:39,120 --> 00:17:41,280 RISK BENEFITS, PML, THE RISK OF 502 00:17:41,280 --> 00:17:44,360 GETTING PML, IS THAT SOMETHING 503 00:17:44,360 --> 00:17:46,080 YOU'RE WILLING TO TRADE OFF IN 504 00:17:46,080 --> 00:17:47,280 EXCHANGE FOR MAYBE HAVING YOUR 505 00:17:47,280 --> 00:17:51,800 DISEASE UNDER CONTROL. 506 00:17:51,800 --> 00:17:55,760 SO AGAIN, IT'S A LIFETIME'S 507 00:17:55,760 --> 00:17:56,760 WORTH OF WORK WHEN YOU GET ONE 508 00:17:56,760 --> 00:17:57,600 OF THESE PREGNANCIES. 509 00:17:57,600 --> 00:18:01,440 >> YOU WERE ON BENVISTA TO HELP 510 00:18:01,440 --> 00:18:03,760 WITH SOME OF YOUR SYMPTOMS BUT 511 00:18:03,760 --> 00:18:04,800 THAT CREATED IMMUNOSUPPRESSION 512 00:18:04,800 --> 00:18:06,640 AND THEN WE ENTER THE COVID ERA, 513 00:18:06,640 --> 00:18:09,200 SO HOW DID THAT AFFECT YOUR 514 00:18:09,200 --> 00:18:09,840 DECISION-MAKING AND HOW TO MEET 515 00:18:09,840 --> 00:18:10,440 THAT CHALLENGE? 516 00:18:10,440 --> 00:18:12,280 >> WELL, I THINK EVERYONE HAD A 517 00:18:12,280 --> 00:18:13,360 CERTAIN BASELINE OF CONCERN AND 518 00:18:13,360 --> 00:18:14,640 WORRY DURING THE PANDEMIC AND 519 00:18:14,640 --> 00:18:18,160 FOR SOMEONE WHO'S 520 00:18:18,160 --> 00:18:18,840 IMMUNOSUPPRESSED, THERE'S AN 521 00:18:18,840 --> 00:18:25,040 ADDED LAYER ON THAT CAKE. 522 00:18:25,040 --> 00:18:29,520 WHEN VACCINES BECAME AVAILABLE, 523 00:18:29,520 --> 00:18:31,640 I WAS CHOMPING AT THE BIT TO GET 524 00:18:31,640 --> 00:18:33,200 ONE, BUT I KNEW I WOULD NEED TO 525 00:18:33,200 --> 00:18:35,640 DO THAT RESEARCH ON MY OWN. 526 00:18:35,640 --> 00:18:41,040 SO MUCH OF CHRONIC ILLNESS IS 527 00:18:41,040 --> 00:18:42,200 MANAGED OUTSIDE OF A CLINICAL 528 00:18:42,200 --> 00:18:42,520 ENCOUNTER. 529 00:18:42,520 --> 00:18:44,160 THERE'S MONTHS THAT GO BY WHERE 530 00:18:44,160 --> 00:18:45,480 YOU NEED TO BE EDUCATING 531 00:18:45,480 --> 00:18:45,760 YOURSELF. 532 00:18:45,760 --> 00:18:47,560 SO I DID A LOT OF WORK TO MAKE 533 00:18:47,560 --> 00:18:50,440 SURE THAT AN MRNA VACCINE WAS 534 00:18:50,440 --> 00:18:53,120 SAFE AND, OF COURSE, THEN SELF 535 00:18:53,120 --> 00:18:54,760 ADVOCATING TO GET A BOOSTER WHEN 536 00:18:54,760 --> 00:18:59,040 THOSE BECAME AVAILABLE, NOT ALL 537 00:18:59,040 --> 00:19:00,040 IMMUNOSUPPRESSED PEOPLE FALL 538 00:19:00,040 --> 00:19:02,840 INTO THE SAME BUCKET, AND SO 539 00:19:02,840 --> 00:19:04,160 UNDERSTANDING THOSE GRADATIONS, 540 00:19:04,160 --> 00:19:05,320 NAVIGATING THAT. 541 00:19:05,320 --> 00:19:07,400 AND JUST THIS LAST WEEK, THE CDC 542 00:19:07,400 --> 00:19:08,640 CAME OUT AND RECOMMENDED 543 00:19:08,640 --> 00:19:10,440 POTENTIALLY A FOURTH SHOT. 544 00:19:10,440 --> 00:19:13,240 SO YOU KNOW, THE LIST OF WORK 545 00:19:13,240 --> 00:19:18,880 AND TASKS GOES ON. 546 00:19:18,880 --> 00:19:20,120 >> SO LASTLY, JENNIFER, MAYBE 547 00:19:20,120 --> 00:19:21,760 YOU CAN SAY JUST A WORD ABOUT 548 00:19:21,760 --> 00:19:22,240 WHAT PARTICIPATING AND 549 00:19:22,240 --> 00:19:23,200 CONTRIBUTING TO RESEARCH HAS 550 00:19:23,200 --> 00:19:23,720 MEANT FOR ME. 551 00:19:23,720 --> 00:19:26,680 I WANT TO SAY THAT I WAS JUST 552 00:19:26,680 --> 00:19:27,920 THRILLED TO HAVE THE OPPORTUNITY 553 00:19:27,920 --> 00:19:30,280 TO RECRUIT YOU TO OUR RESEARCH 554 00:19:30,280 --> 00:19:31,760 TEAM EARLY ON. 555 00:19:31,760 --> 00:19:33,400 YOU CONTRIBUTED SO MUCH BECAUSE 556 00:19:33,400 --> 00:19:35,680 OF YOUR PERSPECTIVE AS A PATIENT 557 00:19:35,680 --> 00:19:37,080 WHO WAS EXPERIENCING THIS 558 00:19:37,080 --> 00:19:38,640 ILLNESS, AND I JUST HAVE REALLY 559 00:19:38,640 --> 00:19:39,840 VALUED OUR RELATIONSHIP OVER 560 00:19:39,840 --> 00:19:40,640 MANY OF THOSE YEARS. 561 00:19:40,640 --> 00:19:41,880 SO MAYBE YOU COULD SHARE A 562 00:19:41,880 --> 00:19:43,240 LITTLE BIT OF THAT WITH THE 563 00:19:43,240 --> 00:19:44,600 AUDIENCE, AND THEN I THINK WE'LL 564 00:19:44,600 --> 00:19:46,960 HAVE TIME FOR SOME QUESTIONS 565 00:19:46,960 --> 00:19:49,680 BEFORE WE MOVE ON AFTER THAT. 566 00:19:49,680 --> 00:19:54,840 >> THANK YOU. 567 00:19:54,840 --> 00:19:57,320 WELL, AS YOU KNOW, I STUMBLED ON 568 00:19:57,320 --> 00:19:59,040 YOUR RESEARCH STUDIES 23 YEARS 569 00:19:59,040 --> 00:20:00,240 AGO AND ENROLLED, AND IT CHANGED 570 00:20:00,240 --> 00:20:01,920 MY LIFE. 571 00:20:01,920 --> 00:20:04,800 PERSONALLY, WHEN YOU GET A 572 00:20:04,800 --> 00:20:05,840 DIAGNOSIS LIKE SYSTEMIC LUPUS 573 00:20:05,840 --> 00:20:08,120 AND ARE TOLD NO CHILDREN AND ARE 574 00:20:08,120 --> 00:20:09,640 TOLD, YOU KNOW, THAT YOU'LL HAVE 575 00:20:09,640 --> 00:20:12,400 TO JUST LIVE WITH A HIGH RISK OF 576 00:20:12,400 --> 00:20:15,200 STROKE, IT TAKES AWAY A LOT OF 577 00:20:15,200 --> 00:20:15,400 HOPE. 578 00:20:15,400 --> 00:20:18,240 AND I FOUND THAT TAKING PART IN 579 00:20:18,240 --> 00:20:20,440 RESEARCH AS A PATIENT RESTORED 580 00:20:20,440 --> 00:20:22,240 MY HOPE. 581 00:20:22,240 --> 00:20:24,400 MY HOPE THAT THINGS WOULD 582 00:20:24,400 --> 00:20:24,720 IMPROVE. 583 00:20:24,720 --> 00:20:26,560 AND IT ALSO GAVE ME A SENSE OF 584 00:20:26,560 --> 00:20:28,960 CONTROL THAT EVEN IF WE 585 00:20:28,960 --> 00:20:30,200 DEPARTMENT HAVE A CURE, I COULD 586 00:20:30,200 --> 00:20:31,600 HELP MOVE THE BALL DOWN FIELD IN 587 00:20:31,600 --> 00:20:35,600 TERMS OF GETTING CLOSER. 588 00:20:35,600 --> 00:20:36,520 PROFESSIONALLY AS A 589 00:20:36,520 --> 00:20:39,320 COMMUNICATIONS PROFESSIONAL, I 590 00:20:39,320 --> 00:20:41,400 CHANGED MY CAREER 23 YEARS AGO 591 00:20:41,400 --> 00:20:44,960 TO FOCUS EXCLUSIVELY ON MAKING 592 00:20:44,960 --> 00:20:46,520 RESEARCH MORE UNDERSTANDABLE, 593 00:20:46,520 --> 00:20:50,240 MORE ACCESSIBLE TO PEOPLE, AND I 594 00:20:50,240 --> 00:20:51,720 SPENT THE LAST 23 YEARS DOING 595 00:20:51,720 --> 00:20:52,600 JUST THAT. 596 00:20:52,600 --> 00:20:54,880 SO IT'S SOMETHING I REMAIN 597 00:20:54,880 --> 00:20:55,440 COMMITTED TO. 598 00:20:55,440 --> 00:20:57,680 IT IS NOT LOST ON ME THAT MY 599 00:20:57,680 --> 00:20:59,960 TWIN DAUGHTERS ARE NOW THE SAME 600 00:20:59,960 --> 00:21:02,840 AGE, 20, THAT I WAS WHEN I WAS 601 00:21:02,840 --> 00:21:03,120 DIAGNOSED. 602 00:21:03,120 --> 00:21:04,280 I KNOW THERE'S A GENETIC 603 00:21:04,280 --> 00:21:05,400 COMPONENT AND I KNOW WE STILL 604 00:21:05,400 --> 00:21:07,800 DON'T HAVE A CURE. 605 00:21:07,800 --> 00:21:10,480 THAT SAID, I KNOW WE HAVE NEW 606 00:21:10,480 --> 00:21:12,440 MEDICATIONS COMING OUT, RESEARCH 607 00:21:12,440 --> 00:21:14,560 CONTINUES, AND MY HOPE IS THAT 608 00:21:14,560 --> 00:21:16,320 AS MUCH AS COVID INVOLVES THE 609 00:21:16,320 --> 00:21:18,920 IMMUNE SYSTEM, MAYBE BY CHANCE, 610 00:21:18,920 --> 00:21:20,600 THIS PANDEMIC WILL LEAD TO 611 00:21:20,600 --> 00:21:23,400 ADDITIONAL UNDERSTANDING OF THE 612 00:21:23,400 --> 00:21:24,880 ROLE IMMUNE SYSTEM PLAYS IN 613 00:21:24,880 --> 00:21:25,120 ILLNESS. 614 00:21:25,120 --> 00:21:27,320 SO I REMAIN VERY OPTIMISTIC AND 615 00:21:27,320 --> 00:21:29,280 AS COMMITTED AS EVER TO 616 00:21:29,280 --> 00:21:29,560 RESEARCH. 617 00:21:29,560 --> 00:21:30,400 >> GREAT. 618 00:21:30,400 --> 00:21:32,480 WELL, THANK YOU SO MUCH FOR 619 00:21:32,480 --> 00:21:33,360 SHARING YOUR STORY, AND I'M 620 00:21:33,360 --> 00:21:35,360 GOING TO TURN THINGS OVER TO DAN 621 00:21:35,360 --> 00:21:37,160 NOW, I THINK, FOR -- IN CASE 622 00:21:37,160 --> 00:21:38,240 SOME QUESTIONS HAVE COME UP THAT 623 00:21:38,240 --> 00:21:39,440 MAYBE YOU CAN ADDRESS AT THIS 624 00:21:39,440 --> 00:21:42,200 TIME. 625 00:21:42,200 --> 00:21:45,840 >> YES, THEUZ VERY , THANK YOU VERY MUCH, 626 00:21:45,840 --> 00:21:47,120 BOTH JENNIFER AND LINDSEY FOR 627 00:21:47,120 --> 00:21:50,640 THIS WONDERFUL, WONDERFUL 628 00:21:50,640 --> 00:21:51,400 INTERVIEW. 629 00:21:51,400 --> 00:21:55,040 FOR THE QUESTIONS, ANYONE IN THE 630 00:21:55,040 --> 00:21:56,880 AUDIENCE WHO HAS A QUESTION FOR 631 00:21:56,880 --> 00:22:00,040 JENNIFER, YOU JUST HAVE TO 632 00:22:00,040 --> 00:22:01,600 SUBMIT THE QUESTION TO THE "SEND 633 00:22:01,600 --> 00:22:04,840 LIVE FEEDBACK" OPTION IN THE 634 00:22:04,840 --> 00:22:08,800 VIDEOCAST DISPLAY, AND MY 635 00:22:08,800 --> 00:22:09,760 COLLEAGUE KENNY WILL FORWARD 636 00:22:09,760 --> 00:22:11,480 THOSE QUESTIONS TO ME. 637 00:22:11,480 --> 00:22:13,480 RIGHT NOW I DON'T SEE ANY IN THE 638 00:22:13,480 --> 00:22:16,920 CHAT AT THE MOMENT, BUT 639 00:22:16,920 --> 00:22:17,840 JENNIFER, MAYBE I CAN ASK A 640 00:22:17,840 --> 00:22:19,240 COUPLE OF QUESTIONS WHILE WE'RE 641 00:22:19,240 --> 00:22:22,960 WAITING FOR SOME TO COME IN. 642 00:22:22,960 --> 00:22:27,240 SO THAT WAS REALLY A VERY, VERY 643 00:22:27,240 --> 00:22:30,440 MOVING AND RIVETTING ACCOUNT OF 644 00:22:30,440 --> 00:22:30,800 WHAT HAPPENED. 645 00:22:30,800 --> 00:22:33,040 CAN YOU TELL US A LITTLE BIT 646 00:22:33,040 --> 00:22:35,880 MORE ABOUT OVER THE COURSE YOUR 647 00:22:35,880 --> 00:22:37,960 ILLNESS, WHAT ABOUT LUPUS HAS 648 00:22:37,960 --> 00:22:40,040 HAD THE BIGGEST IMPACT ON YOUR 649 00:22:40,040 --> 00:22:43,560 LIFE? 650 00:22:43,560 --> 00:22:48,240 >> I THINK THE FACT THAT LUPUS 651 00:22:48,240 --> 00:22:52,200 HAS SO MANY DIFFERENT -- IT'S 652 00:22:52,200 --> 00:22:55,280 CHARACTERIZED BY FLARE AND 653 00:22:55,280 --> 00:22:56,640 REMISSION, AND STRESS CAN CAUSE 654 00:22:56,640 --> 00:22:58,280 THE DISEASE TO FLARE. 655 00:22:58,280 --> 00:23:02,560 WHO AMONG US DOESN'T EXPERIENCE 656 00:23:02,560 --> 00:23:02,800 STRESS? 657 00:23:02,800 --> 00:23:05,800 AND SO I THINK ASIDE FROM 658 00:23:05,800 --> 00:23:06,880 DEALING WITH SOME OF THE 659 00:23:06,880 --> 00:23:09,960 PHYSICAL CHALLENGES AROUND 660 00:23:09,960 --> 00:23:12,800 ARTHRITIS PAIN, WHICH CAN BE 661 00:23:12,800 --> 00:23:13,640 SIGNIFICANT AND GET IN THE WAY 662 00:23:13,640 --> 00:23:19,000 OF SORT OF ACTIVITIES OF DAILY 663 00:23:19,000 --> 00:23:20,000 LIVING, THE FACT THAT ONE NEEDS 664 00:23:20,000 --> 00:23:23,880 TO CONSTANTLY MONITOR EXPOSURES 665 00:23:23,880 --> 00:23:25,440 TO SUN, I LIVE IN CALIFORNIA, 666 00:23:25,440 --> 00:23:28,800 THAT CAN BE A CHALLENGE, STRESS, 667 00:23:28,800 --> 00:23:31,360 BUT HOW DO YOU BALANCE THAT WITH 668 00:23:31,360 --> 00:23:32,480 LIVING A FULL LIFE? 669 00:23:32,480 --> 00:23:38,240 HOW DO YOU BALANCE THAT WITH 670 00:23:38,240 --> 00:23:40,320 KNOWING THAT YOU COULD HAVE A 671 00:23:40,320 --> 00:23:40,960 STROKE. 672 00:23:40,960 --> 00:23:44,400 YOU JUST HAVE TO INTEGRATE IT 673 00:23:44,400 --> 00:23:45,360 INTO YOUR LIFE. 674 00:23:45,360 --> 00:23:47,080 IT'S LIKE AN UNWANTED GUEST THAT 675 00:23:47,080 --> 00:23:48,880 MOVES IN, AND YOU JUST NEED TO 676 00:23:48,880 --> 00:23:50,640 LEARN TO ACCOMMODATE IT. 677 00:23:50,640 --> 00:23:54,120 SO I WILL SAY MENTALLY IT CAN 678 00:23:54,120 --> 00:23:56,440 BE -- IT CAN TAKE A TOLL ON YOUR 679 00:23:56,440 --> 00:23:59,160 MENTAL HEALTH, AND I HAD 680 00:23:59,160 --> 00:24:00,960 PARTICULARLY EARLY ON, A 681 00:24:00,960 --> 00:24:02,240 STRUGGLED WITH DEPRESSION, 682 00:24:02,240 --> 00:24:03,720 TRYING TO FIGURE OUT HOW TO LEAD 683 00:24:03,720 --> 00:24:06,200 THE LIFE I WANTED TO WHILE 684 00:24:06,200 --> 00:24:07,760 HAVING THIS DISEASE. 685 00:24:07,760 --> 00:24:10,080 >> YES, I CAN IMAGINE. 686 00:24:10,080 --> 00:24:12,160 AT LEAST FROM MY RECOLLECTION, 687 00:24:12,160 --> 00:24:15,160 YOU SAID THAT YOU WERE DIAGNOSED 688 00:24:15,160 --> 00:24:17,720 AT THE END OF YOUR SECOND YEAR 689 00:24:17,720 --> 00:24:19,400 OF COLLEGE, SO THERE WERE 690 00:24:19,400 --> 00:24:20,360 PROBABLY SIGNIFICANT STRESSES 691 00:24:20,360 --> 00:24:23,240 JUST IN TERMS OF EXAMS AND 692 00:24:23,240 --> 00:24:25,440 VARIOUS DEADLINES THAT YOU HAD 693 00:24:25,440 --> 00:24:30,520 AS PART OF COLLEGE AND I CAN 694 00:24:30,520 --> 00:24:31,760 JUST IMAGINE PSYCHOLOGICALLY IF 695 00:24:31,760 --> 00:24:32,640 YOU START TO THINK THAT THE 696 00:24:32,640 --> 00:24:36,040 STRESS IS GOING TO INDUCE A 697 00:24:36,040 --> 00:24:38,840 FLARE-UP, THEN YOU GET STRESSED 698 00:24:38,840 --> 00:24:46,440 WORRYING ABOUT THE STRESS. 699 00:24:46,440 --> 00:24:47,000 >> SPOT ON. 700 00:24:47,000 --> 00:24:48,400 IT'S A VICIOUS CYCLE. 701 00:24:48,400 --> 00:24:49,960 >> WHILE WE WERE TALKING, 702 00:24:49,960 --> 00:24:53,000 SOMEONE HAS SENT US A QUESTION. 703 00:24:53,000 --> 00:24:54,920 AND IT IS: HOW IMPORTANT IS TO 704 00:24:54,920 --> 00:24:57,560 JENNIFER THAT RESEARCH BE HONEST 705 00:24:57,560 --> 00:25:05,400 WITH ITS SUBJECTS? 706 00:25:05,400 --> 00:25:06,560 GIVING YOU SOME FEEDBACK IN 707 00:25:06,560 --> 00:25:07,360 TERMS OF THE RESULTS AND WHAT 708 00:25:07,360 --> 00:25:09,320 THEY MEAN, WHETHER THEY BE 709 00:25:09,320 --> 00:25:14,240 PROMISING OR NOT PROMISING. 710 00:25:14,240 --> 00:25:19,120 >> IT'S ABC LIGHT ESSENTIAL ABSOLUTELY ES SENTIAL, 711 00:25:19,120 --> 00:25:20,240 AND I WANT TO ACKNOWLEDGE 712 00:25:20,240 --> 00:25:21,360 SOMETHING THAT DR. CRISWELL 713 00:25:21,360 --> 00:25:22,760 SAID, WHICH IS THAT SHE SAW IT 714 00:25:22,760 --> 00:25:23,760 AS A PRIORITY TO INVOLVE 715 00:25:23,760 --> 00:25:25,080 PATIENTS IN RESEARCH, AND I 716 00:25:25,080 --> 00:25:28,280 THINK WHEN PATIENTS ARE SEEN AS 717 00:25:28,280 --> 00:25:33,120 CO-PARTNERS IN RESEARCH, I NOPA 718 00:25:33,120 --> 00:25:36,240 CORY DOES I KNOW 719 00:25:36,240 --> 00:25:39,040 PCORI DOES A GREAT JOB OF THE 720 00:25:39,040 --> 00:25:39,240 MODEL. 721 00:25:39,240 --> 00:25:40,200 PATIENTS ARE CAPABLE, THEY'RE 722 00:25:40,200 --> 00:25:41,040 THE ONES LIVING WITH THE 723 00:25:41,040 --> 00:25:42,760 DISEASE, THEY CAN HANDLE THAT 724 00:25:42,760 --> 00:25:42,960 NEWS. 725 00:25:42,960 --> 00:25:45,280 AND I THINK BEING HONEST BUT 726 00:25:45,280 --> 00:25:46,960 HAVING AN EVOLVING RELATIONSHIP 727 00:25:46,960 --> 00:25:49,040 WITH A PATIENT DURING THE STUDY, 728 00:25:49,040 --> 00:25:52,400 NOT JUST RECRUITMENT BUT 729 00:25:52,400 --> 00:25:54,960 FOCUSING ON RETENTION AND 730 00:25:54,960 --> 00:25:56,640 INFORMATION, HAVING THAT OPEN 731 00:25:56,640 --> 00:25:59,640 TRANSPARENT DIALOGUE IS 732 00:25:59,640 --> 00:26:03,560 ESSENTIAL. 733 00:26:03,560 --> 00:26:05,200 >> YES, I CERTAINLY AGREE WITH 734 00:26:05,200 --> 00:26:05,480 THAT. 735 00:26:05,480 --> 00:26:06,720 HOW ABOUT PATIENT ADVOCACY 736 00:26:06,720 --> 00:26:06,960 GROUPS? 737 00:26:06,960 --> 00:26:08,320 HAVE YOU BEEN INVOLVED IN THEM? 738 00:26:08,320 --> 00:26:09,480 IT SOUNDS LIKE PROBABLY YOU 739 00:26:09,480 --> 00:26:11,800 HAVE, AND WHAT IS THE ROLE OF 740 00:26:11,800 --> 00:26:13,320 THAT, IN THE WHOLE PROCESS OF 741 00:26:13,320 --> 00:26:18,440 LIVING WITH A CHRONIC DISEASE. 742 00:26:18,440 --> 00:26:20,000 >> I WAS HEAVILY INVOLVED IN 743 00:26:20,000 --> 00:26:21,520 PATIENT ADVOCACY GROUPS, 744 00:26:21,520 --> 00:26:22,840 PARTICULARLY WHEN I WAS WORKING 745 00:26:22,840 --> 00:26:25,720 ON DR. CRISWELL'S STUDIES 746 00:26:25,720 --> 00:26:27,440 BECAUSE THEY CAN BE SUCH A RICH 747 00:26:27,440 --> 00:26:31,800 SOURCE OF RECRUITMENT FOR 748 00:26:31,800 --> 00:26:32,200 RESEARCH. 749 00:26:32,200 --> 00:26:34,080 I CAN TELL YOU I SUBSCRIBE TO 750 00:26:34,080 --> 00:26:35,640 MANY DIFFERENT LUPUS FOUNDATION 751 00:26:35,640 --> 00:26:39,080 OF AMERICA, THE AUTOIMMUNE 752 00:26:39,080 --> 00:26:41,640 DISEASE SOCIETY NEWSLETTERS JUST 753 00:26:41,640 --> 00:26:43,760 TO SAY INFORMED. 754 00:26:43,760 --> 00:26:45,120 I REFERENCE THE FACT A LOT OF 755 00:26:45,120 --> 00:26:46,960 THE WORK FALLS ON PATIENTS, SO 756 00:26:46,960 --> 00:26:48,760 ONE THING I'LL STRESS IS THESE 757 00:26:48,760 --> 00:26:49,240 ADD VO 758 00:26:49,240 --> 00:26:54,440 ADVOCACY GROUPS DO A GREAT JOB 759 00:26:54,440 --> 00:26:55,040 OF COMMUNICATING IN PLAIN 760 00:26:55,040 --> 00:26:55,360 LANGUAGE. 761 00:26:55,360 --> 00:26:57,360 THAT IS THE EMPHASIS OF MY 762 00:26:57,360 --> 00:26:58,440 PROFESSIONAL LIFE BUT IT IS 763 00:26:58,440 --> 00:27:00,640 ABSOLUTELY ESSENTIAL TO HELP 764 00:27:00,640 --> 00:27:02,360 PEOPLE BE ENGAGED BECAUSE IF YOU 765 00:27:02,360 --> 00:27:03,640 CAN'T UNDERSTAND, YOU CANNOT BE 766 00:27:03,640 --> 00:27:04,520 ENGAGED. 767 00:27:04,520 --> 00:27:10,200 >> YES, AND A LOT OF TIMES THE 768 00:27:10,200 --> 00:27:11,560 MEDICAL JARGON, EVEN IF THE 769 00:27:11,560 --> 00:27:12,240 PHYSICIANS THINK THAT THEY'RE 770 00:27:12,240 --> 00:27:14,040 SPEAKING IN PLAIN LANGUAGE, IT 771 00:27:14,040 --> 00:27:15,840 MAY BE PLAIN TO THEM BUT NOT TO 772 00:27:15,840 --> 00:27:23,640 ANYBODY ELSE. 773 00:27:23,640 --> 00:27:25,400 CAN YOU SPEAK TO SOME OF THE 774 00:27:25,400 --> 00:27:26,200 BIGGEST COMMUNICATION ISSUES 775 00:27:26,200 --> 00:27:30,800 BETWEEN PATIENTS WITH LUPUS AND 776 00:27:30,800 --> 00:27:35,200 PHYSICIANS? 777 00:27:35,200 --> 00:27:35,840 >> JARGON. 778 00:27:35,840 --> 00:27:37,640 I WILL SAY THIS, THE NUMBER ONE 779 00:27:37,640 --> 00:27:39,520 PIECE OF ADVICE I CAN GIVE AND 780 00:27:39,520 --> 00:27:41,160 HAVE GIVEN OVER THE YEARS AS A 781 00:27:41,160 --> 00:27:42,360 PATIENT ADVOCATE IS TO NOT BE 782 00:27:42,360 --> 00:27:45,960 AFRAID OR ASHAMED TO SAY I DON'T 783 00:27:45,960 --> 00:27:46,960 UNDERSTAND, CAN YOU SAY THAT 784 00:27:46,960 --> 00:27:51,160 AGAIN IN PLAIN LANGUAGE. 785 00:27:51,160 --> 00:27:54,000 IT IS ABC ABSOLUTELY ESSENTIAL IF 786 00:27:54,000 --> 00:27:56,120 YOU WANT A PATIENT TO BE ABLE TO 787 00:27:56,120 --> 00:28:04,640 LEAVE YOUR OFFICE AND -- I HATE 788 00:28:04,640 --> 00:28:06,320 USING THE WORD ADHERE, BUT TAKE 789 00:28:06,320 --> 00:28:08,040 THE MEDICATION, GO GET THE TESTS 790 00:28:08,040 --> 00:28:09,040 DONE, THERE HAS TO BE 791 00:28:09,040 --> 00:28:11,440 UNDERSTANDING, THERE HAS TO BE 792 00:28:11,440 --> 00:28:12,040 BUY-IN. 793 00:28:12,040 --> 00:28:13,240 SO IF YOU DON'T HAVE A PROVIDER 794 00:28:13,240 --> 00:28:14,400 THAT'S SKILLED IN PLAIN 795 00:28:14,400 --> 00:28:17,120 LANGUAGE, DON'T BE AFRAID TO ASK 796 00:28:17,120 --> 00:28:21,440 FOR THAT, AND ALSO EMPLOYING 797 00:28:21,440 --> 00:28:23,040 TEACHBACK, SAYING AS A PATIENT, 798 00:28:23,040 --> 00:28:24,240 HERE'S WHAT I HEARD YOU SAY, IS 799 00:28:24,240 --> 00:28:25,160 THIS CORRECT, IS THIS WHAT I 800 00:28:25,160 --> 00:28:25,800 NEED TO DO. 801 00:28:25,800 --> 00:28:26,800 AND PROVIDERS SHOULD BE DOING 802 00:28:26,800 --> 00:28:33,720 THAT AS WELL. 803 00:28:33,720 --> 00:28:35,440 >> SO THOSE ARE VERY WISE PIECES 804 00:28:35,440 --> 00:28:35,760 OF ADVICE. 805 00:28:35,760 --> 00:28:37,000 SO WE HAVE A COUPLE MORE 806 00:28:37,000 --> 00:28:38,400 QUESTIONS AND THEN I THINK WE'LL 807 00:28:38,400 --> 00:28:39,840 MOVE THINGS BACK TO 808 00:28:39,840 --> 00:28:40,960 DR. CRISWELL, AND THERE WILL BE 809 00:28:40,960 --> 00:28:42,680 OPPORTUNITY AT THE END FOR 810 00:28:42,680 --> 00:28:45,240 PEOPLE TO ASK QUESTIONS AS WELL. 811 00:28:45,240 --> 00:28:49,560 BUT QUESTION NUMBER THREE IS 812 00:28:49,560 --> 00:28:51,320 WHAT HAS BEEN THE VALUABLE 813 00:28:51,320 --> 00:28:53,040 STRATEGY IN MANAGING THE IDEA 814 00:28:53,040 --> 00:28:54,720 THAT YOU CANNOT ESCAPE SOMETHING 815 00:28:54,720 --> 00:28:56,840 THAT IS INHERENT IN YOUR OWN 816 00:28:56,840 --> 00:28:57,440 BODY. 817 00:28:57,440 --> 00:28:59,680 HAVE YOU FOUND MEDITATION, 818 00:28:59,680 --> 00:29:03,800 THERAPY OR SOMETHING ELSE 819 00:29:03,800 --> 00:29:04,040 HELPFUL? 820 00:29:04,040 --> 00:29:05,840 >> WE HAVE TOO MUCH STIGMA IN 821 00:29:05,840 --> 00:29:07,760 THIS COUNTRY AROUND MENTAL 822 00:29:07,760 --> 00:29:12,600 HEALTH, SO I HESITATE TO SHARE, 823 00:29:12,600 --> 00:29:14,880 I SOUGHT THERAPY TO HELP ME 824 00:29:14,880 --> 00:29:19,160 LEARN COPING MECHANISMS STO 825 00:29:19,160 --> 00:29:21,560 LEARN TO BE AT PIECE WITH IT. 826 00:29:21,560 --> 00:29:22,480 YOU CAN'T FIGHT SOMETHING THAT'S 827 00:29:22,480 --> 00:29:26,520 IN YOUR BODY AND AVOID BEING 828 00:29:26,520 --> 00:29:29,200 STRESSED AND DRIVEN TO THE 829 00:29:29,200 --> 00:29:29,440 BREAK. 830 00:29:29,440 --> 00:29:37,840 SO I HAD TO LEARN TO COPE AND 831 00:29:37,840 --> 00:29:39,240 DEVELOP A MORE RESPECTFUL 832 00:29:39,240 --> 00:29:40,280 RELATIONSHIP WITH THE DISEASE 833 00:29:40,280 --> 00:29:41,760 HAS CERTAIN NEEDS, SOMETIMES I 834 00:29:41,760 --> 00:29:43,040 HAVE TO PAUSE AND TEND TO THE 835 00:29:43,040 --> 00:29:43,440 DISEASE'S NEEDS. 836 00:29:43,440 --> 00:29:45,960 BUT IT DOESN'T MEAN THAT THOSE 837 00:29:45,960 --> 00:29:46,920 NEEDS ARE PARAMOUNT AND OVERRIDE 838 00:29:46,920 --> 00:29:52,760 WHAT I WANT TO DO. 839 00:29:52,760 --> 00:29:53,920 IT'S A LITTLE BIT OF A TRADEOFF 840 00:29:53,920 --> 00:29:55,480 BUT I CAN TELL YOU 30 YEARS IN, 841 00:29:55,480 --> 00:29:56,960 IT IS AN ONGOING PROCESS, AND 842 00:29:56,960 --> 00:29:59,040 CAN STILL BE A STRUGGLE. 843 00:29:59,040 --> 00:30:00,960 >> YEAH, THAT'S FOR SURE. 844 00:30:00,960 --> 00:30:01,320 OKAY. 845 00:30:01,320 --> 00:30:03,240 WELL, I'LL JUST ASK THE LAST OF 846 00:30:03,240 --> 00:30:04,960 THE QUESTIONS NOW THAT'S COME 847 00:30:04,960 --> 00:30:05,960 IN. 848 00:30:05,960 --> 00:30:07,040 GIVEN THAT ELECTRONIC RECORDS 849 00:30:07,040 --> 00:30:09,320 ARE COMMONLY AVAILABLE, WHAT DO 850 00:30:09,320 --> 00:30:11,760 YOU SEE AS THE IMPEDIMENT TO 851 00:30:11,760 --> 00:30:13,600 THEIR UNIFORM ADOPTION AND THE 852 00:30:13,600 --> 00:30:16,320 NEED FOR THE PATIENT TO SHOULDER 853 00:30:16,320 --> 00:30:17,200 THE RESPONSIBILITY TO TRANSFER 854 00:30:17,200 --> 00:30:20,800 THEIR OWN RECORDS? 855 00:30:20,800 --> 00:30:23,040 WHY CAN'T WE JUST HAVE A GOOD 856 00:30:23,040 --> 00:30:23,920 ELECTRONIC MEDICAL RECORD SYSTEM 857 00:30:23,920 --> 00:30:25,960 THAT IS UNIVERSALLY APPLIED? 858 00:30:25,960 --> 00:30:30,080 >> SUCH A SIMPLE CONCEPT. 859 00:30:30,080 --> 00:30:32,640 WE HEAR THE TERM 860 00:30:32,640 --> 00:30:35,440 INTEROPERABILITY THROWN OUT A 861 00:30:35,440 --> 00:30:36,840 LOT AND OCCASIONALLY YOU HEAR 862 00:30:36,840 --> 00:30:37,760 PEOPLE SAY WE'RE THERE ALREADY. 863 00:30:37,760 --> 00:30:39,040 I'M GOING TO USE AN EXAMPLE, I'M 864 00:30:39,040 --> 00:30:40,400 GOING TO NAME A NAME HERE, AND 865 00:30:40,400 --> 00:30:40,920 THAT'S HE PICK. 866 00:30:40,920 --> 00:30:42,640 FOR EXAMPLE, MANY OF THE HEALTH 867 00:30:42,640 --> 00:30:43,920 SYSTEMS ARE IN EPIC. 868 00:30:43,920 --> 00:30:46,040 IN THE COURSE OF FOUR YEARS, I 869 00:30:46,040 --> 00:30:47,840 WAS AT THREE DIFFERENT HEALTH 870 00:30:47,840 --> 00:30:49,760 SYSTEMS, ALL USED EPIC. 871 00:30:49,760 --> 00:30:53,520 AND MY RECORDS WERE NEVER FULLY 872 00:30:53,520 --> 00:30:55,320 INTEGRATED BECAUSE IT IS AT THE 873 00:30:55,320 --> 00:30:57,240 HEALTH SYSTEM LEVEL, THIS 874 00:30:57,240 --> 00:31:02,880 HESITANCY TO PULL IN ALL OF THAT 875 00:31:02,880 --> 00:31:05,240 DATA FROM HEALTH SYSTEM A WHEN 876 00:31:05,240 --> 00:31:06,560 YOU'RE AT HEALTH SYSTEM B. 877 00:31:06,560 --> 00:31:08,760 I UNDERSTAND IT'S TECHNICALLY 878 00:31:08,760 --> 00:31:09,840 POSSIBLE BUT SHOULD A PROVIDER 879 00:31:09,840 --> 00:31:11,360 BE SPENDING THEIR PRECIOUS TIME 880 00:31:11,360 --> 00:31:11,680 DOING THAT? 881 00:31:11,680 --> 00:31:13,400 SHOULD IT BE AT THE SYSTEM 882 00:31:13,400 --> 00:31:14,120 LEVEL? 883 00:31:14,120 --> 00:31:17,360 WE NEED SYSTEMS TO REALLY COMMIT 884 00:31:17,360 --> 00:31:25,240 TO MAKING THAT EASIER THAT THAT 885 00:31:25,240 --> 00:31:26,040 INFORMATION IS PRESENT SO DOCTOR 886 00:31:26,040 --> 00:31:27,840 AND PATIENT CAN MAKE THE BEST 887 00:31:27,840 --> 00:31:31,040 SHARED DECISIONS DURING THE 888 00:31:31,040 --> 00:31:32,880 LIMITED TIME THEY HAVE TOGETHER. 889 00:31:32,880 --> 00:31:34,200 >> YEAH, MAKING THE BEST USE OF 890 00:31:34,200 --> 00:31:35,560 THEIR TIME BECAUSE IF YOU SPEND 891 00:31:35,560 --> 00:31:36,960 ALL YOUR TIME FUMBLING AROUND 892 00:31:36,960 --> 00:31:38,840 TRYING TO FIGURE OUT WHAT THE 893 00:31:38,840 --> 00:31:41,880 RECORD SHOWS, THEN IT'S TIME TO 894 00:31:41,880 --> 00:31:42,800 MOVE ON. 895 00:31:42,800 --> 00:31:43,720 THAT'S NOT A GOOD SITUATION AT 896 00:31:43,720 --> 00:31:45,040 ALL. 897 00:31:45,040 --> 00:31:46,320 ALL RIGHT. 898 00:31:46,320 --> 00:31:47,360 WELL, THAT'S IT FOR THE 899 00:31:47,360 --> 00:31:48,960 QUESTIONS THAT WE HAVE. 900 00:31:48,960 --> 00:31:50,400 JENNIFER, THANK YOU SO, SO MUCH. 901 00:31:50,400 --> 00:31:53,240 I REALLY -- WE ALL REALLY 902 00:31:53,240 --> 00:31:55,440 APPRECIATE YOUR BEING HERE AND 903 00:31:55,440 --> 00:31:58,080 IT'S JUST SUCH A IMPORTANT 904 00:31:58,080 --> 00:32:01,200 THING, ESPECIALLY WHEN WE'RE 905 00:32:01,200 --> 00:32:03,560 TALKING ABOUT HUMAN ILLNESS TO 906 00:32:03,560 --> 00:32:04,320 ACTUALLY HAVE -- TO PUT A FACE 907 00:32:04,320 --> 00:32:05,080 ON IT. 908 00:32:05,080 --> 00:32:06,440 SO THANK YOU SO, SO MUCH. 909 00:32:06,440 --> 00:32:11,120 >> THANK YOU. 910 00:32:11,120 --> 00:32:11,600 >> ALL RIGHT. 911 00:32:11,600 --> 00:32:13,040 CAN YOU SEE MY SLIDES AGAIN, 912 00:32:13,040 --> 00:32:14,040 EVERYBODY? 913 00:32:14,040 --> 00:32:14,800 >> YES. 914 00:32:14,800 --> 00:32:16,160 >> AND HEAR ME OKAY? 915 00:32:16,160 --> 00:32:17,160 SO THANKS AGAIN, JENNIFER. 916 00:32:17,160 --> 00:32:21,840 THAT WAS WONDERFUL. 917 00:32:21,840 --> 00:32:25,440 SO AS I MENTIONED, THERE'S NO 918 00:32:25,440 --> 00:32:29,040 PATHOGNOMIC TEST FOR LUPUS. 919 00:32:29,040 --> 00:32:30,440 AND WHAT PHYSICIANS FACE WHEN 920 00:32:30,440 --> 00:32:31,400 TRYING TO DETERMINE WHETHER 921 00:32:31,400 --> 00:32:33,920 INDIVIDUALS HAVE LUPUS IS THEY 922 00:32:33,920 --> 00:32:40,000 CONSIDER A LONG LIST OF 923 00:32:40,000 --> 00:32:41,120 MANIFESTATIONS, CLASSIFICATION 924 00:32:41,120 --> 00:32:42,760 CRITERIA, AND IN THE CASE OF 925 00:32:42,760 --> 00:32:43,880 LUPUS, ALTHOUGH THESE HAVE BEEN 926 00:32:43,880 --> 00:32:45,600 REVISED RECENTLY, THE WAY TO 927 00:32:45,600 --> 00:32:46,640 DETERMINE SOMEONE MEETS CRITERIA 928 00:32:46,640 --> 00:32:48,560 FOR LUPUS IS TO CONSIDER THESE 929 00:32:48,560 --> 00:32:49,560 11 CRITERIA, AND THEN ASK THE 930 00:32:49,560 --> 00:32:50,920 QUESTION, OKAY, WELL, HAVE AT 931 00:32:50,920 --> 00:32:53,600 LEAST FOUR OF THESE BEEN 932 00:32:53,600 --> 00:32:54,600 PRESENT? 933 00:32:54,600 --> 00:32:55,880 AND IF SO, YES, THIS PERSON CAN 934 00:32:55,880 --> 00:32:58,760 BE CLASSIFIED AT LUPUS, THEN IF 935 00:32:58,760 --> 00:32:59,160 NOT, NO. 936 00:32:59,160 --> 00:33:01,240 BUT IT'S EASY TO UNDERSTAND THE 937 00:33:01,240 --> 00:33:02,680 GREAT HETEROGENEITY OF THE 938 00:33:02,680 --> 00:33:04,440 DISEASE WITH SUCH WIDE RANGING 939 00:33:04,440 --> 00:33:05,040 MANIFESTATIONS. 940 00:33:05,040 --> 00:33:07,520 NOW I HIGHLIGHTED IN BOLD THE 941 00:33:07,520 --> 00:33:11,080 MANIFESTATIONS THAT JENNIFER 942 00:33:11,080 --> 00:33:13,000 HAD, SO SHE MET SEVEN OUT OF 943 00:33:13,000 --> 00:33:14,640 THESE 11 BUT HAS NOT HAD ANY 944 00:33:14,640 --> 00:33:15,880 EVIDENCE OF RENAL INVOLVEMENT 945 00:33:15,880 --> 00:33:17,200 OVER 30 YEARS, FOR EXAMPLE, AND 946 00:33:17,200 --> 00:33:18,480 HASN'T EXPERIENCED SOME OF THE 947 00:33:18,480 --> 00:33:19,800 OTHER MANIFESTATIONS. 948 00:33:19,800 --> 00:33:21,560 SO TREMENDOUS HETEROGENEITY AND 949 00:33:21,560 --> 00:33:26,800 CHALLENGES FOR DIAGNOSIS. 950 00:33:26,800 --> 00:33:32,920 SHE ALSO HAD LOW LEVELS LIKELY 951 00:33:32,920 --> 00:33:34,880 RELATED TO THE VERY SERIOUS 952 00:33:34,880 --> 00:33:35,560 PREGNANCY COMPLICATION THAT SHE 953 00:33:35,560 --> 00:33:37,200 HAD, THE HELLP SYNDROME. 954 00:33:37,200 --> 00:33:40,440 SO REALLY COMPLICATED DISEASE. 955 00:33:40,440 --> 00:33:41,880 SO NOW WHAT ABOUT GENETIC 956 00:33:41,880 --> 00:33:42,400 FACTORS? 957 00:33:42,400 --> 00:33:43,760 SOME OF THE EARLIEST INSIGHT TO 958 00:33:43,760 --> 00:33:45,560 THE IMPORTANCE OF GENETICS CAME 959 00:33:45,560 --> 00:33:48,560 FROM TWIN STUDIES. 960 00:33:48,560 --> 00:33:50,600 PICTURED HERE ARE TWO SETS OF 961 00:33:50,600 --> 00:33:51,320 IDENTICAL TWIN GIRLS. 962 00:33:51,320 --> 00:33:53,480 THEY'RE ACTUALLY VERY HEALTHY. 963 00:33:53,480 --> 00:33:55,280 THEY HAPPEN TO BE JENNIFER'S 964 00:33:55,280 --> 00:33:57,120 TWINS IN THE MIDDLE AND MY TWINS 965 00:33:57,120 --> 00:33:58,360 ON THE OUTSIDE. 966 00:33:58,360 --> 00:34:00,960 WE HAD TWINS ABOUT FOUR MONTHS 967 00:34:00,960 --> 00:34:02,000 APART. 968 00:34:02,000 --> 00:34:04,200 AND IT'S STUDIES OF CONCORDANCE 969 00:34:04,200 --> 00:34:07,760 FOR DISEASE IN TWINS THAT GIVES 970 00:34:07,760 --> 00:34:08,840 US SOME INSIGHT INTO THE 971 00:34:08,840 --> 00:34:10,080 STRENGTH OF THE GENETIC 972 00:34:10,080 --> 00:34:11,240 CONTRIBUTION TO LUPUS. 973 00:34:11,240 --> 00:34:13,040 NOW, FOR LUPUS, LIKE MANY 974 00:34:13,040 --> 00:34:15,240 COMPLEX DISEASES, THE 975 00:34:15,240 --> 00:34:16,840 CONCORDANCE FOR THE DISEASE 976 00:34:16,840 --> 00:34:18,760 AMONG IDENTICAL TWINS IS ONLY 977 00:34:18,760 --> 00:34:21,240 ABOUT 20 OR 25%. 978 00:34:21,240 --> 00:34:25,080 SO MUCH OF THE DISEASE RISK 979 00:34:25,080 --> 00:34:30,400 RELATES TO NO KNACK FACTORS OTHER THAN 980 00:34:30,400 --> 00:34:30,640 GENETICS. 981 00:34:30,640 --> 00:34:31,880 THE CONCORDANCE FOR FRATERNAL 982 00:34:31,880 --> 00:34:34,720 TWINS IS MUCH LESS, THE 983 00:34:34,720 --> 00:34:35,960 CONCORDANCE AM SIBLINGS OF AN 984 00:34:35,960 --> 00:34:37,240 AFFECTED INDIVIDUAL, EVEN 985 00:34:37,240 --> 00:34:37,800 SMALLER. 986 00:34:37,800 --> 00:34:41,640 NOW IN SPITE OF THE FACT THAT 987 00:34:41,640 --> 00:34:43,640 GENETICS HAD A CLEAR-CUT ROLE, 988 00:34:43,640 --> 00:34:46,000 IT WAS PAINSTAKINGLY SLOW TO TRY 989 00:34:46,000 --> 00:34:47,040 TO IDENTIFY GENETIC FACTORS 990 00:34:47,040 --> 00:34:48,520 UNTIL IT BECAME POSSIBLE TO 991 00:34:48,520 --> 00:34:49,720 PERFORM GENOME-WIDE ASSOCIATION 992 00:34:49,720 --> 00:34:51,040 STUDIES WHEN WE COULD LOOK AT 993 00:34:51,040 --> 00:34:52,960 LARGE NUMBERS OF VARIANTS IN 994 00:34:52,960 --> 00:34:54,680 WELL CHARACTERIZED SETS OF CASES 995 00:34:54,680 --> 00:34:57,760 AND CONTROLS. 996 00:34:57,760 --> 00:34:59,240 AND FOLLOWING THAT CAPABILITY, 997 00:34:59,240 --> 00:35:00,320 THERE'S BEEN JUST AN EXPLOSION 998 00:35:00,320 --> 00:35:01,440 OF THE IDENTIFICATION OF GENES 999 00:35:01,440 --> 00:35:04,000 FOR LUPUS AND OTHER AUTOIMMUNE 1000 00:35:04,000 --> 00:35:06,680 DISEASES. 1001 00:35:06,680 --> 00:35:09,040 THIS IS A SNAPSHOT FROM A FEW 1002 00:35:09,040 --> 00:35:11,440 YEARS AGO TO SHOW YOU HOW 1003 00:35:11,440 --> 00:35:12,240 RAPIDLY PROGRESS OCCURRED. 1004 00:35:12,240 --> 00:35:14,240 THIS IS A META-ANALYSIS OF 1005 00:35:14,240 --> 00:35:16,000 ALMOST 6,000 LUPUS PATIENTS, 1006 00:35:16,000 --> 00:35:17,640 OVER 13,000 CONTROLS, ALL OF 1007 00:35:17,640 --> 00:35:20,600 EUROPEAN ANCESTRY IN THIS CASE, 1008 00:35:20,600 --> 00:35:21,520 IDENTIFYING 63 RISK SIGNALS. 1009 00:35:21,520 --> 00:35:23,840 AND JUST TO ORIENT YOU TO THIS 1010 00:35:23,840 --> 00:35:25,240 MAN 1011 00:35:25,240 --> 00:35:26,720 MANHATTAN PLOT, EVERY DOT ON THE 1012 00:35:26,720 --> 00:35:28,840 SLIDE IS A GENETIC VARIANT. 1013 00:35:28,840 --> 00:35:29,840 THE STRENGTH OF THE ASSOCIATION 1014 00:35:29,840 --> 00:35:34,880 WITH THE DISEASE IS SHOAP ON SHOWN ON THE 1015 00:35:34,880 --> 00:35:35,440 Y AXIS. 1016 00:35:35,440 --> 00:35:36,640 CONTRIBUTIONS FOR MANY, MANY, 1017 00:35:36,640 --> 00:35:37,720 MANY OTHER GENES. 1018 00:35:37,720 --> 00:35:39,800 SOME REALLY STRIKING FINDINGS 1019 00:35:39,800 --> 00:35:45,240 FROM THE EMERGING TB. WAS EMERGING STUDIE S IN 1020 00:35:45,240 --> 00:35:48,320 LUPUS AND OTHER DISEASES, IT WAS 1021 00:35:48,320 --> 00:35:50,760 POSSIBLE TO IDENTIFY A LARGE 1022 00:35:50,760 --> 00:35:52,040 NUMBER OF GENES IN A SINGLE 1023 00:35:52,040 --> 00:35:52,520 EXPERIMENT. 1024 00:35:52,520 --> 00:35:54,520 ALL OF THESE LOCI WERE IDENTIFY 1025 00:35:54,520 --> 00:35:55,760 JUST IN THE CONTEXT OF THAT 1026 00:35:55,760 --> 00:35:57,440 SINGLE STUDY, BUT MANY OF THEM, 1027 00:35:57,440 --> 00:36:00,160 MORE THAN HALF, WERE BEING 1028 00:36:00,160 --> 00:36:01,800 IDENTIFIED IN THE CONTEXT OF 1029 00:36:01,800 --> 00:36:04,960 GWAS STUDIES OF OTHER AUTOIMMUNE 1030 00:36:04,960 --> 00:36:07,800 DISEASES, EVEN THOSE WITH VERY 1031 00:36:07,800 --> 00:36:08,640 DIFFERENT CLINICAL 1032 00:36:08,640 --> 00:36:09,120 MANIFESTATIONS. 1033 00:36:09,120 --> 00:36:12,080 SO A LOT OF SHARED RISK ACROSS 1034 00:36:12,080 --> 00:36:12,840 VERY HETEROGENEOUS SETS OF 1035 00:36:12,840 --> 00:36:14,120 DISEASES. 1036 00:36:14,120 --> 00:36:17,440 ANOTHER VERY STRIKING FINDING 1037 00:36:17,440 --> 00:36:20,120 WAS THE THE EXTENT TO WHICH GENES 1038 00:36:20,120 --> 00:36:21,680 RELATED TO THE TOLL LIKE 1039 00:36:21,680 --> 00:36:23,120 RECEPTOR INTERFERON TYPE 1040 00:36:23,120 --> 00:36:25,560 1 SIGNALING PATHWAY, SIMPLIFIED 1041 00:36:25,560 --> 00:36:26,840 AND ILLUSTRATED HERE IN A SIMPLE 1042 00:36:26,840 --> 00:36:28,440 WAY ON THIS SLIDE, WERE BEING 1043 00:36:28,440 --> 00:36:31,560 IDENTIFIED IN GENETIC STU STUDIES. 1044 00:36:31,560 --> 00:36:33,720 VIRTUALLY EVERY GENE WAS 1045 00:36:33,720 --> 00:36:34,240 REPRESENTED HERE HAS BEEN 1046 00:36:34,240 --> 00:36:35,040 DEMONSTRATED TO BE ASSOCIATED 1047 00:36:35,040 --> 00:36:36,320 WITH LUPUS. 1048 00:36:36,320 --> 00:36:41,680 NOW I'M GOING TO HIGHLIGHT, I'LL 1049 00:36:41,680 --> 00:36:44,560 POINT OUT JUST A COUPLE, 1050 00:36:44,560 --> 00:36:47,360 INCLUDING STAT 4 OVER HERE AND 1051 00:36:47,360 --> 00:36:48,440 IRF-5, BUT VIRTUALLY ALL OF 1052 00:36:48,440 --> 00:36:51,800 THESE GENES HAVE BEEN ASSOCIATED 1053 00:36:51,800 --> 00:36:53,200 WITH THE GENETIC CONTRIBUTION TO 1054 00:36:53,200 --> 00:36:53,640 LUPUS. 1055 00:36:53,640 --> 00:36:57,040 NOW, I'VE BEEN TALKING ABOUT THE 1056 00:36:57,040 --> 00:36:59,640 HETEROGENEITY OF THE DISEASE. 1057 00:36:59,640 --> 00:37:01,000 STAPH 4, 1 OF THE VERY FIRST 1058 00:37:01,000 --> 00:37:02,880 GENES TO BE IDENTIFIED IN THE 1059 00:37:02,880 --> 00:37:04,880 LAST DECADE OR SO, PROVIDED US 1060 00:37:04,880 --> 00:37:10,480 WITH GREAT INSIGHT TO THE EXTENT 1061 00:37:10,480 --> 00:37:13,040 TO WHICH GENETIC VARIATIONS 1062 00:37:13,040 --> 00:37:13,480 WOULD VARY. 1063 00:37:13,480 --> 00:37:14,840 WE HAD THE OPPORTUNITY TO LOOK 1064 00:37:14,840 --> 00:37:17,920 AT THE STAT4 RISK VARIANT, FIRST 1065 00:37:17,920 --> 00:37:18,640 IDENTIFIED FOR RHEUMATOID 1066 00:37:18,640 --> 00:37:18,920 ARTHRITIS. 1067 00:37:18,920 --> 00:37:20,760 WE SAID, GEE, IS IT ASSOCIATED 1068 00:37:20,760 --> 00:37:21,240 WITH LUPUS? 1069 00:37:21,240 --> 00:37:24,280 IF SO, PERHAPS ESPECIALLY AMONG 1070 00:37:24,280 --> 00:37:26,440 PATIENTS WITH ARTHRITIS. 1071 00:37:26,440 --> 00:37:30,800 WELL, IN FACT, TRFS THERE WAS NO 1072 00:37:30,800 --> 00:37:33,840 ASSOCIATION WITH LUPUS FOR STAT4 BUT A VER Y STRONG 1073 00:37:33,840 --> 00:37:35,560 ASSOCIATION, LARGE, HIGH ODDS 1074 00:37:35,560 --> 00:37:36,560 RATIOS AMONG INDIVIDUALS WITH 1075 00:37:36,560 --> 00:37:37,720 RENAL DISEASE AND EARLY AGE OF 1076 00:37:37,720 --> 00:37:38,240 ONSET. 1077 00:37:38,240 --> 00:37:39,800 SO THAT GAVE US INSIGHT INTO THE 1078 00:37:39,800 --> 00:37:42,400 EXTENT TO WHICH GENES WOULD 1079 00:37:42,400 --> 00:37:43,440 INFLUENCE THE SPECIFIC 1080 00:37:43,440 --> 00:37:46,240 MANIFESTATIONS PRESENT. 1081 00:37:46,240 --> 00:37:47,600 SO WE OVER THE ENSUING YEARS 1082 00:37:47,600 --> 00:37:51,640 WERE ABLE TO REANALYZE GWA DATA 1083 00:37:51,640 --> 00:37:53,480 BROKEN DOWN FOO SUBSETS OF 1084 00:37:53,480 --> 00:37:54,840 DISEASES, TO TRY TO UNDERSTAND 1085 00:37:54,840 --> 00:37:56,200 THE GENETIC DIFFERENCES. 1086 00:37:56,200 --> 00:37:58,160 WHAT I'VE SHOWN HERE ARE TWO 1087 00:37:58,160 --> 00:38:00,000 MANHATTAN PLOTS NOW, FROM THREE 1088 00:38:00,000 --> 00:38:01,640 STUDIES WHERE WE'RE LOOKING JUST 1089 00:38:01,640 --> 00:38:03,680 AT DOUBLE STRANDED DNA POSITIVE 1090 00:38:03,680 --> 00:38:07,000 PATIENTS HERE AND ONLY A DOUBLE 1091 00:38:07,000 --> 00:38:08,000 STRANDED DNA NEGATIVE PATIENT 1092 00:38:08,000 --> 00:38:09,040 HERE, AND YOU CAN SEE THE 1093 00:38:09,040 --> 00:38:10,160 STRIKING DIFFERENCES IN THE 1094 00:38:10,160 --> 00:38:13,000 GENETIC CONTRIBUTION TO THESE 1095 00:38:13,000 --> 00:38:14,080 DISEASES. 1096 00:38:14,080 --> 00:38:19,000 HUGE MAC CONTRIBUTION, CRACKS 1097 00:38:19,000 --> 00:38:24,560 FROM STAT 4, VERY MODEST 1098 00:38:24,560 --> 00:38:26,080 ASSOCIATION WITH DOUBLE STRAND 1099 00:38:26,080 --> 00:38:26,480 NEGATIVE DISEASE. 1100 00:38:26,480 --> 00:38:28,240 WE ALSO LOOKED AT RENAL DISEASE. 1101 00:38:28,240 --> 00:38:29,640 HERE WE'RE ASKING ONCE YOU HAVE 1102 00:38:29,640 --> 00:38:30,920 LUPUS, WHAT ARE THE GENES THAT 1103 00:38:30,920 --> 00:38:32,680 ARE GOING TO INFLUENCE WHETHER 1104 00:38:32,680 --> 00:38:35,720 OR NOT YOU DEVELOP SIGNIFICANT 1105 00:38:35,720 --> 00:38:38,040 RENAL INVOLVEMENT, A REALLY 1106 00:38:38,040 --> 00:38:38,520 FEARED MANIFESTATION. 1107 00:38:38,520 --> 00:38:42,720 WHAT WAS SURPRISING HERE WAS THE 1108 00:38:42,720 --> 00:38:44,280 EXTENT TO WHICH THE GENES THAT 1109 00:38:44,280 --> 00:38:45,400 CONTRIBUTED TO DEVELOPMENT OF 1110 00:38:45,400 --> 00:38:46,440 NEPHRITIS ARE DISTINCT FROM 1111 00:38:46,440 --> 00:38:47,760 THOSE THAT INFLUENCE YOUR 1112 00:38:47,760 --> 00:38:48,960 OVERALL RISK OF LUPUS. 1113 00:38:48,960 --> 00:38:51,400 NOTICE THE VERY MODEST HLA 1114 00:38:51,400 --> 00:38:52,720 CONTRIBUTION, AND MANY OTHER 1115 00:38:52,720 --> 00:38:54,200 GENES THAT WEREN'T ON OUR RADAR 1116 00:38:54,200 --> 00:38:55,440 SCREEN FROM THE CASE CONTROL 1117 00:38:55,440 --> 00:39:00,640 STUDIES. 1118 00:39:00,640 --> 00:39:01,680 IT ALSO BECAME POSSIBLE TO ASK, 1119 00:39:01,680 --> 00:39:03,360 WHAT IS THE INFLUENCE OF THE 1120 00:39:03,360 --> 00:39:05,240 NUMBER OF RISK VARIANTS AN 1121 00:39:05,240 --> 00:39:08,720 INDIVIDUAL HAS INHERITED? 1122 00:39:08,720 --> 00:39:09,680 WHEN WE LOOKED AT INDIVIDUALS 1123 00:39:09,680 --> 00:39:10,920 ACCORDING TO THE NUMBER OF 1124 00:39:10,920 --> 00:39:12,560 ESTABLISHED RISK VARIANTS AND WE 1125 00:39:12,560 --> 00:39:15,480 ASKED, WHAT WERE THEIR DISEASE 1126 00:39:15,480 --> 00:39:16,680 CHARACTERISTICS, IT WAS 1127 00:39:16,680 --> 00:39:18,240 STRIKING, THE EXTENT TO WHICH 1128 00:39:18,240 --> 00:39:18,920 CERTAIN DISEASE MANIFESTATIONS 1129 00:39:18,920 --> 00:39:22,200 SUCH AS DOUBLE STRANDED DNA 1130 00:39:22,200 --> 00:39:23,600 ANTIBODIES, OTHER IMMUNOLOGIC 1131 00:39:23,600 --> 00:39:24,240 MANIFESTATIONS, RENAL DISEASE TO 1132 00:39:24,240 --> 00:39:26,440 A CERTAIN EXTENT, WERE INCREASED 1133 00:39:26,440 --> 00:39:27,400 AM 1134 00:39:27,400 --> 00:39:29,960 AMONG THOSE WITH A HIGH GENETIC 1135 00:39:29,960 --> 00:39:31,640 BURDEN, A HIGH NUMBER OF RISK 1136 00:39:31,640 --> 00:39:32,680 VARIANTS, WHEREAS OTHER 1137 00:39:32,680 --> 00:39:35,000 MANIFESTATIONS WERE NOT 1138 00:39:35,000 --> 00:39:38,040 INCREASED SIGNIFICANTLY AMONG 1139 00:39:38,040 --> 00:39:40,280 INDIVIDUALS WITH A LARGE GENETIC 1140 00:39:40,280 --> 00:39:45,040 RISK SCORE. 1141 00:39:45,040 --> 00:39:46,560 SO WE KNOW GENETICS IS NOT THE 1142 00:39:46,560 --> 00:39:47,080 ENTIRE ANSWER. 1143 00:39:47,080 --> 00:39:48,280 THERE'S BEEN A LONG HISTORY OF 1144 00:39:48,280 --> 00:39:49,320 STUDIES OF ENVIRONMENTAL FACTORS 1145 00:39:49,320 --> 00:39:50,600 THAT CONTRIBUTE TO THE DISEASE, 1146 00:39:50,600 --> 00:39:51,600 BUT RESEARCH IN THAT AREA IS 1147 00:39:51,600 --> 00:39:53,360 VERY CHALLENGING. 1148 00:39:53,360 --> 00:39:55,360 THAT IN PART HAS PROMPTED 1149 00:39:55,360 --> 00:39:57,600 INTEREST IN LOOKING AT EP GENIC 1150 00:39:57,600 --> 00:39:58,760 GENETIC FACTORS. 1151 00:39:58,760 --> 00:40:00,920 THESE ARE FACTORS THAT INFLUENCE 1152 00:40:00,920 --> 00:40:02,040 GENE EXPRESSION BUT DON'T 1153 00:40:02,040 --> 00:40:05,720 INVOLVE MODIFICATIONS TO THE DNA 1154 00:40:05,720 --> 00:40:06,200 NUCLEOTIDE SEQUENCE. 1155 00:40:06,200 --> 00:40:08,360 I'M GOING TO FOCUS ON DNA 1156 00:40:08,360 --> 00:40:09,240 METHYLATION BECAUSE OF ITS LINK 1157 00:40:09,240 --> 00:40:12,560 TO THE ENVIRONMENT. 1158 00:40:12,560 --> 00:40:13,880 BUT THE HOPE HERE IS THAT EB 1159 00:40:13,880 --> 00:40:15,640 GENETIC FACTORS HELP TO EXPLAIN 1160 00:40:15,640 --> 00:40:18,240 NOT ONLY THIS MISSING 1161 00:40:18,240 --> 00:40:19,760 HERITABILITY, NOT DEFINED BY 1162 00:40:19,760 --> 00:40:24,200 GENETIC RISK VARIANTS, BUT ALSO 1163 00:40:24,200 --> 00:40:25,440 HELP TO FILL OUT THE TOTALITY OF 1164 00:40:25,440 --> 00:40:26,320 THE CONTRIBUTION TO THE DISEASE. 1165 00:40:26,320 --> 00:40:28,880 THIS IS CONSISTENT WITH A 1166 00:40:28,880 --> 00:40:30,280 LONG-STANDING MODEL IN WHICH 1167 00:40:30,280 --> 00:40:36,920 GENETIC PREDISPOSITION OVER TIME 1168 00:40:36,920 --> 00:40:37,800 EVENTUALLY LEADS TO DISEASE IN 1169 00:40:37,800 --> 00:40:39,040 THE CONTEXT OF APPROPRIATE 1170 00:40:39,040 --> 00:40:40,960 ENVIRONMENTAL FACTORS, PERHAPS 1171 00:40:40,960 --> 00:40:42,920 MEDIATED BY EPIGENETIC 1172 00:40:42,920 --> 00:40:44,600 MODIFICATION. 1173 00:40:44,600 --> 00:40:47,040 SO WHY LOOK AT DNA METHYLATION? 1174 00:40:47,040 --> 00:40:49,040 WELL, IT HAS PROFOUND INFLUENCES 1175 00:40:49,040 --> 00:40:51,560 ON GENE EXPRESSION, AND IT'S 1176 00:40:51,560 --> 00:40:52,760 BOTH INHERITED AND ALSO AFFECTED 1177 00:40:52,760 --> 00:40:54,280 BY THE ENVIRONMENT. 1178 00:40:54,280 --> 00:40:56,800 DNA METHYLATION OCCURS AT THESE 1179 00:40:56,800 --> 00:41:00,360 SO CALLED GPC SITES, WHERE YOU 1180 00:41:00,360 --> 00:41:02,200 HAVE CYTOSINE FOLLOWED BY A 1181 00:41:02,200 --> 00:41:03,000 GUANINE. 1182 00:41:03,000 --> 00:41:04,280 IT INFLUENCES LEVELS OF GENE 1183 00:41:04,280 --> 00:41:05,640 EXPRESSION. 1184 00:41:05,640 --> 00:41:07,800 NOW THE VERY FIRST BACK TO TWINS 1185 00:41:07,800 --> 00:41:08,640 AGAIN, THE VERY FIRST 1186 00:41:08,640 --> 00:41:11,280 METHYLATION STUDY IN LUPUS WAS A 1187 00:41:11,280 --> 00:41:15,040 SMALL STUDY COMPARING DISCORDANT 1188 00:41:15,040 --> 00:41:16,920 IDENTICAL TWINS, FIVE SETS OF 1189 00:41:16,920 --> 00:41:18,720 IDENTICAL TWINS, DISCORDANT FOR 1190 00:41:18,720 --> 00:41:21,200 THE DISEASE, AND A SET OF FIVE 1191 00:41:21,200 --> 00:41:23,040 MATCH CONTROL INDIVIDUALS. 1192 00:41:23,040 --> 00:41:24,600 WHAT THE INVESTIGATORS DID HERE 1193 00:41:24,600 --> 00:41:27,000 A DECADE AGO NOW IS THEY LOOKED 1194 00:41:27,000 --> 00:41:28,280 AT 800 METHYLATION SITES ACROSS 1195 00:41:28,280 --> 00:41:29,520 THE GENOME AND THEY COMPARED 1196 00:41:29,520 --> 00:41:31,960 LEVELS OF DNA METHYLATION STATUS 1197 00:41:31,960 --> 00:41:35,640 BETWEEN THE TWO TWINS WITH AND 1198 00:41:35,640 --> 00:41:38,000 WITHOUT LUPUS AND THE HEALTHY 1199 00:41:38,000 --> 00:41:38,240 CONTROLS. 1200 00:41:38,240 --> 00:41:39,560 OVERALL, THE LUPUS TWINS HAD 1201 00:41:39,560 --> 00:41:46,360 MUCH LOWER LEVELS OF METHYLATION 1202 00:41:46,360 --> 00:41:48,200 GLOBALLY AND 50 GENES, MANY OF 1203 00:41:48,200 --> 00:41:49,840 WHICH HAVE ROLES IN THE IMMUNE 1204 00:41:49,840 --> 00:41:50,040 SYSTEM. 1205 00:41:50,040 --> 00:41:51,160 SO RESEARCH IN THIS AREA 1206 00:41:51,160 --> 00:41:53,160 PROGRESSED RAPIDLY, LOOKING AT 1207 00:41:53,160 --> 00:41:55,040 GREATER AND GREATER NUMBER OF 1208 00:41:55,040 --> 00:41:57,360 CPG SITES, 28,000 METHYLATION 1209 00:41:57,360 --> 00:42:00,120 SITES IN THIS STUDY, LARGER SETS 1210 00:42:00,120 --> 00:42:03,760 OF INDIVIDUALS WITH A SIMILAR 1211 00:42:03,760 --> 00:42:05,560 PATTERN. 1212 00:42:05,560 --> 00:42:06,880 SIGNIFICANTLY DIFFERENTIALLY 1213 00:42:06,880 --> 00:42:08,280 METHYLATED GENE REGIONS BETWEEN 1214 00:42:08,280 --> 00:42:10,520 LUPUS AND CONTROL INDIVIDUALS, 1215 00:42:10,520 --> 00:42:12,400 OFTEN HIGHLIGHTING GENES 1216 00:42:12,400 --> 00:42:14,200 RELEVANT TO THE IMMUNE SYSTEM 1217 00:42:14,200 --> 00:42:19,440 AND INFLAMMATORY PATHWAYS. 1218 00:42:19,440 --> 00:42:23,160 NOW THE BIGGEST OF THESE SO 1219 00:42:23,160 --> 00:42:24,840 CALLED EWA STUDIES WAS A SWEDISH 1220 00:42:24,840 --> 00:42:30,960 STUDY LOOKING AT 450,000 CPG 1221 00:42:30,960 --> 00:42:33,560 SITES. 1222 00:42:33,560 --> 00:42:35,200 72,000 -- 7200 DIFFERENTIALLY 1223 00:42:35,200 --> 00:42:36,720 METHYLATED SITES, MANY IN THE 1224 00:42:36,720 --> 00:42:40,760 TYPE 1 INTERFERON GENES, AND 1225 00:42:40,760 --> 00:42:48,480 MANY INFLUENCED BY GENETIC 1226 00:42:48,480 --> 00:42:49,640 VARIATION, AND SOME OF THOSE 1227 00:42:49,640 --> 00:42:54,240 GENES CORE CORRESPONDED TO RISK LOCI. 1228 00:42:54,240 --> 00:42:56,960 NOW WHAT ABOUT DNA METHYLATION 1229 00:42:56,960 --> 00:42:57,520 AND DISEASE MANIFESTATIONS? 1230 00:42:57,520 --> 00:43:00,600 I SHARED SOME WORK IN THE 1231 00:43:00,600 --> 00:43:01,640 GENETIC STUDIES SHOWING HOW 1232 00:43:01,640 --> 00:43:04,080 DIFFERENT THE GENETIC 1233 00:43:04,080 --> 00:43:07,880 CONTRIBUTION IS ACCORDING TO THE 1234 00:43:07,880 --> 00:43:09,000 CLINICAL MANIFESTATIONS. 1235 00:43:09,000 --> 00:43:11,040 WHAT ABOUT DNA METHYLATION 1236 00:43:11,040 --> 00:43:11,600 PATTERNS? 1237 00:43:11,600 --> 00:43:15,840 WE'VE NOW HAD THE OPPORTUNITY TO 1238 00:43:15,840 --> 00:43:18,760 PERFORM EPIGENOME-WIDE 1239 00:43:18,760 --> 00:43:19,960 ASSOCIATION STUDIES IN WELL 1240 00:43:19,960 --> 00:43:20,680 CHARACTERIZED INDIVIDUALS WITH 1241 00:43:20,680 --> 00:43:22,720 LUPUS SO THAT WE CAN ASK WHETHER 1242 00:43:22,720 --> 00:43:24,560 PATTERNS OF DNA METHYLATION ARE 1243 00:43:24,560 --> 00:43:25,040 DIFFERENT. 1244 00:43:25,040 --> 00:43:26,160 FOR EXAMPLE, BETWEEN INDIVIDUALS 1245 00:43:26,160 --> 00:43:30,320 WITH DOUBLE STRANDED DNA 1246 00:43:30,320 --> 00:43:32,720 POSITIVE DISEASE AND DOUBLE 1247 00:43:32,720 --> 00:43:33,920 STRANDED DNA NEGATIVE DISEASE. 1248 00:43:33,920 --> 00:43:35,720 THIS SLIDE SUMMARIZES RESULTS 1249 00:43:35,720 --> 00:43:37,760 FOR OVER 300 SUCH INDIVIDUALS. 1250 00:43:37,760 --> 00:43:39,400 WHAT'S BEEN STRIKING TO US IS 1251 00:43:39,400 --> 00:43:42,120 NOT ONLY THE NUMBER OF 1252 00:43:42,120 --> 00:43:43,000 STATISTICALLY SIGNIFICANT 1253 00:43:43,000 --> 00:43:44,280 METHYLATION DIFFERENCES BETWEEN 1254 00:43:44,280 --> 00:43:45,760 THESE SUBSETS OF THE DISEASE, 1255 00:43:45,760 --> 00:43:48,880 BUT THE NUMBER THAT HAD NOT -- 1256 00:43:48,880 --> 00:43:49,840 THAT HIGHLIGHT GENE REGIONS THAT 1257 00:43:49,840 --> 00:43:51,280 WERE NOT ON OUR RADAR SCREEN 1258 00:43:51,280 --> 00:43:54,160 FROM GENETIC STUDIES, ALSO 1259 00:43:54,160 --> 00:43:57,200 PROMINENCE OF TYPE I INTERFERON 1260 00:43:57,200 --> 00:43:59,400 BETWEEN GENES, AND THE MODEST 1261 00:43:59,400 --> 00:44:00,640 CONTRIBUTION OF THE MHC REGION 1262 00:44:00,640 --> 00:44:01,840 COMPARED TO GENETIC STUDIES. 1263 00:44:01,840 --> 00:44:04,200 SO WE'VE LOOKED AT AUTO ANTIBODY 1264 00:44:04,200 --> 00:44:05,840 PROFILES, WE'VE LOOKED AT RENAL 1265 00:44:05,840 --> 00:44:06,160 DISEASE. 1266 00:44:06,160 --> 00:44:08,640 ONCE AGAIN, A VERY IMPORTANT 1267 00:44:08,640 --> 00:44:12,440 DISEASE MANIFESTATION, WE SEE 1268 00:44:12,440 --> 00:44:15,760 ALMOST 20 SIGNIFICANTLY 1269 00:44:15,760 --> 00:44:18,840 DIFFERENTIAL -- PATIENTS THAT DO 1270 00:44:18,840 --> 00:44:19,880 AND DON'T DEVELOP RENAL DISEASE. 1271 00:44:19,880 --> 00:44:21,760 IN THIS CASE, THE GENE REGIONS 1272 00:44:21,760 --> 00:44:23,760 THAT ARE DIFFERENTIALLY 1273 00:44:23,760 --> 00:44:25,400 METHYLATED HIGHLIGHT PATHWAYS 1274 00:44:25,400 --> 00:44:28,240 RELATED TO TISSUE HYPOXIA AND 1275 00:44:28,240 --> 00:44:32,640 TYPE 1 INTERFERON RESPONSES. 1276 00:44:32,640 --> 00:44:34,040 SO AS YOU CAN IMAGINE, TO 1277 00:44:34,040 --> 00:44:35,720 CONTINUE WORK IN THIS AREA, IT'S 1278 00:44:35,720 --> 00:44:36,520 CRITICALLY IMPORTANT TO HAVE 1279 00:44:36,520 --> 00:44:40,360 ACCESS TO DEEPLY PHENOTYPE 1280 00:44:40,360 --> 00:44:45,040 INDIVIDUAL. 1281 00:44:45,040 --> 00:44:47,400 FORTUNATE TO UTILIZE A DEEPLY 1282 00:44:47,400 --> 00:44:49,800 PHENOTYPED MULTIETHNIC COHORT 1283 00:44:49,800 --> 00:44:53,200 THAT WAS DEVELOPED THANKS TO 1284 00:44:53,200 --> 00:44:54,920 FUNDING FROM THE CENTERS FOR 1285 00:44:54,920 --> 00:44:55,560 DISEASE CONTROL AND PREVENTION 1286 00:44:55,560 --> 00:44:58,240 AND LED BY MY COLLEAGUES AT 1287 00:44:58,240 --> 00:45:00,840 UCSF, AND WE HAVE BEEN 1288 00:45:00,840 --> 00:45:02,320 CHARACTERIZING THESE INDIVIDUALS 1289 00:45:02,320 --> 00:45:04,440 FOR GENOME-WIDE GENETICS, 1290 00:45:04,440 --> 00:45:07,080 EPIGENETICS, AND OTHER OMICS TO 1291 00:45:07,080 --> 00:45:09,440 HELP US BETTER UNDERSTAND 1292 00:45:09,440 --> 00:45:13,160 HETEROGENEITY OF THE DISEASE, 1293 00:45:13,160 --> 00:45:14,960 INCLUDING GREATER INSIGHT INTO 1294 00:45:14,960 --> 00:45:16,560 THE RACE AND ETHNIC DIFFERENCES 1295 00:45:16,560 --> 00:45:18,520 IN THE DISEASE. 1296 00:45:18,520 --> 00:45:19,960 SO I'LL VERY BRIEFLY SUMMARIZE 1297 00:45:19,960 --> 00:45:21,720 SOME OF OUR WORK RELATED TO THE 1298 00:45:21,720 --> 00:45:28,440 CLUES COHORT. 1299 00:45:28,440 --> 00:45:30,320 WE DECIDED INSTEAD OF LOOKING 1300 00:45:30,320 --> 00:45:31,520 INDIVIDUAL DISEASE 1301 00:45:31,520 --> 00:45:32,280 MANIFESTATIONS, WE KNOW MANY ARE 1302 00:45:32,280 --> 00:45:34,640 CORRELATED WITH EACH OA THEY 1303 00:45:34,640 --> 00:45:35,040 CLUSTER TOGETHER. 1304 00:45:35,040 --> 00:45:36,760 SO WE CONSIDERED ALL THE ACR 1305 00:45:36,760 --> 00:45:38,080 CRITERIA AND THE SUBCRITERIA 1306 00:45:38,080 --> 00:45:42,320 THAT HAD BEEN CHARACTERIZED FOR 1307 00:45:42,320 --> 00:45:43,760 INDIVIDUALS AND WE ASKED WHETHER 1308 00:45:43,760 --> 00:45:47,640 THERE WERE NATURAL CLUSTERS OF 1309 00:45:47,640 --> 00:45:51,000 INDIVIDUALS BASED ON BE THESE 1310 00:45:51,000 --> 00:45:51,360 MANIFESTATIONS. 1311 00:45:51,360 --> 00:45:52,160 INDEED THREE CLUSTERS EMERGED 1312 00:45:52,160 --> 00:45:58,120 FROM THE DATA, WHICH WE HAVE 1313 00:45:58,120 --> 00:45:59,120 LABELED MILD BECAUSE OF THE 1314 00:45:59,120 --> 00:46:01,120 ABSENCE OF SIGNIFICANT INTERNAL 1315 00:46:01,120 --> 00:46:04,040 ORGAN INVOLVEMENT AND TWO THAT 1316 00:46:04,040 --> 00:46:06,240 ARE PRIMARILY DIFFERENT IN TERMS 1317 00:46:06,240 --> 00:46:07,640 OF HEMATOLOGIC MANIFESTATIONS. 1318 00:46:07,640 --> 00:46:09,240 SO BOTH HAVE SIGNIFICANT RENAL 1319 00:46:09,240 --> 00:46:11,240 INVOLVEMENT BUT THEY DIFFER IN 1320 00:46:11,240 --> 00:46:13,000 TERMS OF THE HEMATOLOGIC 1321 00:46:13,000 --> 00:46:13,520 MANIFESTATION. 1322 00:46:13,520 --> 00:46:15,000 SO THREE CLUSTERS OF INDIVIDUALS 1323 00:46:15,000 --> 00:46:17,440 BASED ON THE PATTERNS OF THESE 1324 00:46:17,440 --> 00:46:18,040 MANY MANIFESTATIONS. 1325 00:46:18,040 --> 00:46:21,200 SO THEN WE ASKED THE QUESTION, 1326 00:46:21,200 --> 00:46:22,320 WELL, DO THESE CLUSTERS DIFFER 1327 00:46:22,320 --> 00:46:23,720 IN TERMS OF THEIR METHYLATION 1328 00:46:23,720 --> 00:46:24,440 PATTERNS. 1329 00:46:24,440 --> 00:46:25,840 LOOKING GENOME-WIDE AND 1330 00:46:25,840 --> 00:46:27,320 ACCOUNTING FOR OTHER FACTORS 1331 00:46:27,320 --> 00:46:29,200 THAT WOULD INFLUENCE METHYLATION 1332 00:46:29,200 --> 00:46:36,240 STATUS, AGE, SPOKING STATUS, 1333 00:46:36,240 --> 00:46:42,120 CELL COMPETITION, ET CETERA, WE 1334 00:46:42,120 --> 00:46:43,080 FOUND -- ONCE AGAIN MANY OF 1335 00:46:43,080 --> 00:46:44,800 WHICH MAPPED TO THE TYPE 1336 00:46:44,800 --> 00:46:45,680 1 INTERFERON PATHWAY. 1337 00:46:45,680 --> 00:46:47,360 FORTUNATELY WE HAD ACCESS TO AN 1338 00:46:47,360 --> 00:46:48,240 INDEPENDENT COHORT THAT ALLOWED 1339 00:46:48,240 --> 00:46:51,080 US TO CONFIRM THESE ASSOCIATIONS 1340 00:46:51,080 --> 00:46:53,440 BETWEEN DNA METHYLATION STATUS 1341 00:46:53,440 --> 00:46:55,120 AND CLINICAL CLUSTERS. 1342 00:46:55,120 --> 00:46:59,480 NOW WE CAN ALSO LEVERAGE THIS 1343 00:46:59,480 --> 00:47:02,280 DATA BY MAPPING THOSE 256 SITES 1344 00:47:02,280 --> 00:47:04,160 TO GENES AND THEN PERFORMING 1345 00:47:04,160 --> 00:47:04,840 PATHWAY ANALYSIS. 1346 00:47:04,840 --> 00:47:07,040 THAT SORT OF ANALYSIS 1347 00:47:07,040 --> 00:47:07,840 DEMONSTRATES SIGNIFICANT 1348 00:47:07,840 --> 00:47:08,800 ENRICHMENT OF GENES ASSOCIATED 1349 00:47:08,800 --> 00:47:10,960 WITH INTERFERON TYPE 1350 00:47:10,960 --> 00:47:12,240 1 SIGNALING, ANTIVIRAL 1351 00:47:12,240 --> 00:47:13,160 RESPONSES, AND NUMEROUS 1352 00:47:13,160 --> 00:47:14,920 INFLAMMATORY PATHWAYS. 1353 00:47:14,920 --> 00:47:16,640 NOW ONCE AGAIN, AS I'VE 1354 00:47:16,640 --> 00:47:18,440 HIGHLIGHTED, MANY OF THE GENE 1355 00:47:18,440 --> 00:47:19,720 REGIONS HIGHLIGHTED METHYLATION 1356 00:47:19,720 --> 00:47:22,040 STUDIES ARE DISTINCT FROM THOSE 1357 00:47:22,040 --> 00:47:23,840 THAT WE SEE IN ASSOCIATION 1358 00:47:23,840 --> 00:47:25,280 STUDIES, GIVING US ANOTHER 1359 00:47:25,280 --> 00:47:26,120 PERSPECTIVE ON CONTRIBUTIONS TO 1360 00:47:26,120 --> 00:47:28,840 THE DISEASE. 1361 00:47:28,840 --> 00:47:30,360 SO NOW ONCE AGAIN I'VE BEEN 1362 00:47:30,360 --> 00:47:32,680 FOCUSING ON DNA METHYLATION AS 1363 00:47:32,680 --> 00:47:34,960 AN IMPORTANT CLUE TO THE 1364 00:47:34,960 --> 00:47:35,680 ENVIRONMENT FOR CONTRIBUTION TO 1365 00:47:35,680 --> 00:47:36,320 THE DISEASE. 1366 00:47:36,320 --> 00:47:39,800 WHY IS THAT? 1367 00:47:39,800 --> 00:47:41,360 PATTERNS OF DNA METHYLATION ARE 1368 00:47:41,360 --> 00:47:42,880 GENERALLY STABLE, BUT THEY CAN 1369 00:47:42,880 --> 00:47:43,240 BE INTERRUPTED. 1370 00:47:43,240 --> 00:47:45,800 FOR EXAMPLE, AS A RESULT OF 1371 00:47:45,800 --> 00:47:47,360 OXIDATIVE STRESS OR OTHER 1372 00:47:47,360 --> 00:47:49,640 ENVIRONMENTAL EXPOSURES. 1373 00:47:49,640 --> 00:47:52,520 AND THERE'S A LONG HISTORY OF 1374 00:47:52,520 --> 00:47:54,360 ENVIRONMENTAL TRIGGERS FOR 1375 00:47:54,360 --> 00:47:54,560 LUPUS. 1376 00:47:54,560 --> 00:47:56,320 AND IT'S VERY DIFFICULT IN THE 1377 00:47:56,320 --> 00:47:58,200 CONTEXT OF THESE EPIDEMIOLOGIC 1378 00:47:58,200 --> 00:48:00,040 AND OBSERVATION STUDIES TO 1379 00:48:00,040 --> 00:48:01,360 REALLY DEMONSTRATE CAUSATION, 1380 00:48:01,360 --> 00:48:03,160 NOT TO MENTION TO UNDERSTAND 1381 00:48:03,160 --> 00:48:04,400 UNDERLYING MECHANISMS. 1382 00:48:04,400 --> 00:48:08,160 SO THERE'S GREAT HOPE THAT 1383 00:48:08,160 --> 00:48:12,000 EPIGENETIC CHANGE WILL EXPLAIN 1384 00:48:12,000 --> 00:48:12,880 SOME OF THESE ENVIRONMENTAL 1385 00:48:12,880 --> 00:48:13,640 ASSOCIATIONS WITH THE DISEASE 1386 00:48:13,640 --> 00:48:15,240 AND THAT FURTHER ANALYSIS OF 1387 00:48:15,240 --> 00:48:16,920 EPIGENETIC PATTERNS WILL PROVIDE 1388 00:48:16,920 --> 00:48:18,120 GREATER INSIGHT INTO OTHER 1389 00:48:18,120 --> 00:48:20,240 ENVIRONMENTAL CONTRIBUTIONS TO 1390 00:48:20,240 --> 00:48:20,680 THE DISEASE. 1391 00:48:20,680 --> 00:48:22,120 AND IN FACT, THERE'S A LOT OF 1392 00:48:22,120 --> 00:48:24,200 INTEREST IN THIS AREA, AND A 1393 00:48:24,200 --> 00:48:27,200 NUMBER OF EXPOSURES THAT HAVE 1394 00:48:27,200 --> 00:48:28,720 BEEN IMPLICATED IN STUDIES OF 1395 00:48:28,720 --> 00:48:30,440 LUPUS HAVE NOW BEEN SHOWN TO BE 1396 00:48:30,440 --> 00:48:32,360 ASSOCIATED WITH DNA METHYLATION 1397 00:48:32,360 --> 00:48:33,040 CHANGES. 1398 00:48:33,040 --> 00:48:35,560 PROVIDING PROMISE THAT THIS IS 1399 00:48:35,560 --> 00:48:36,840 GOING TO BE AN INFORMATIVE AREA 1400 00:48:36,840 --> 00:48:37,640 OF FUTURE RESEARCH. 1401 00:48:37,640 --> 00:48:39,120 I WOULD DRAW YOUR ATTENTION TO 1402 00:48:39,120 --> 00:48:41,680 THIS REALLY NICE REVIEW OF THE 1403 00:48:41,680 --> 00:48:46,280 SUBJECT RECENTLY BY CHRISTINA 1404 00:48:46,280 --> 00:48:47,040 LINATA AND COLLEAGUES. 1405 00:48:47,040 --> 00:48:48,480 NOW LASTLY, I'VE ALLUDED TO THE 1406 00:48:48,480 --> 00:48:50,320 FACT THAT IT'S CHALLENGING TO 1407 00:48:50,320 --> 00:48:51,440 UNDERSTAND THE ENVIRONMENTAL 1408 00:48:51,440 --> 00:48:53,760 CONTRIBUTION TO THE DISEASE. 1409 00:48:53,760 --> 00:48:55,480 BUT THERE'S RENEWED INTEREST IN 1410 00:48:55,480 --> 00:48:57,680 THIS CONCEPT OF THE EXPOSOME 1411 00:48:57,680 --> 00:48:59,240 THAT'S MEANT TO REFLECT THE 1412 00:48:59,240 --> 00:49:02,440 TOTALITY OF EXPOSURES ACROSS THE 1413 00:49:02,440 --> 00:49:03,880 LIFE COURSE, INCLUDING ALL SORTS 1414 00:49:03,880 --> 00:49:07,600 OF EXTERNAL AND INTERNAL 1415 00:49:07,600 --> 00:49:08,040 EXPOSURES. 1416 00:49:08,040 --> 00:49:10,000 THE HOPE IS THAT BY 1417 00:49:10,000 --> 00:49:12,200 CHARACTERIZING THE EXPOSOME IN 1418 00:49:12,200 --> 00:49:13,920 HEALTH AND DISEASE, WE CAN HAVE 1419 00:49:13,920 --> 00:49:15,520 A MORE COMPREHENSIVE AND 1420 00:49:15,520 --> 00:49:18,080 ACCURATE WAY OF UNDERSTANDING 1421 00:49:18,080 --> 00:49:19,000 HOW THE ENVIRONMENT CONTRIBUTES 1422 00:49:19,000 --> 00:49:21,560 TO THE DISEASE INCLUDING THE 1423 00:49:21,560 --> 00:49:22,880 RELATIONSHIP TO EPIGENETIC 1424 00:49:22,880 --> 00:49:23,120 FACTORS. 1425 00:49:23,120 --> 00:49:24,320 SO WE'RE REALLY EXCITED ABOUT 1426 00:49:24,320 --> 00:49:26,920 THE FACT THAT THERE ARE NOW 1427 00:49:26,920 --> 00:49:29,800 NON-TARGETED APPROACHES TO VERY 1428 00:49:29,800 --> 00:49:32,960 COMPREHENSIVELY CHARACTERIZE THE 1429 00:49:32,960 --> 00:49:35,040 EXPOSOME IN LUPUS AND OTHER 1430 00:49:35,040 --> 00:49:36,240 AUTOIMMUNE DISEASES AND WE'RE 1431 00:49:36,240 --> 00:49:37,240 EXCITED TO SEE HOW THOSE 1432 00:49:37,240 --> 00:49:38,640 STUDIES, WHAT THEY TELL US ABOUT 1433 00:49:38,640 --> 00:49:41,440 THE DISEASE LUPUS. 1434 00:49:41,440 --> 00:49:42,760 SO LET ME JUST CONCLUDE MY 1435 00:49:42,760 --> 00:49:44,840 COMMENTS BY THANKING MY MANY 1436 00:49:44,840 --> 00:49:50,000 COLLEAGUES, ESPECIALLY JOANNE, 1437 00:49:50,000 --> 00:49:52,040 LISA, CHRISTINA, SHARON AND KIM 1438 00:49:52,040 --> 00:49:53,080 WHO CONTRIBUTED VERY IMPORTANTLY 1439 00:49:53,080 --> 00:49:54,360 TO THE STUDIES I MENTIONED, MY 1440 00:49:54,360 --> 00:49:56,400 LONG LIST OF OTHER COLLABORATORS 1441 00:49:56,400 --> 00:50:03,800 FROM AROUND THE WORLD, MANY 1442 00:50:03,800 --> 00:50:05,840 NON-PROFIT ORGANIZATIONS, AND 1443 00:50:05,840 --> 00:50:07,000 PERHAPS MOST IMPORTANTLY, THE 1444 00:50:07,000 --> 00:50:08,320 MANY PATIENTS WITH LUPUS AND 1445 00:50:08,320 --> 00:50:09,840 THEIR FAMILY MEMBERS WHO HAVE 1446 00:50:09,840 --> 00:50:10,520 CONTRIBUTED SO SIGNIFICANTLY TO 1447 00:50:10,520 --> 00:50:13,880 OUR RESEARCH AND PROVIDED SUCH 1448 00:50:13,880 --> 00:50:15,160 GREAT INSPIRATION, AND ONCE 1449 00:50:15,160 --> 00:50:16,640 AGAIN, THANKS TO JENNIFER FOR 1450 00:50:16,640 --> 00:50:21,000 SHARING HER STORY HERE TODAY. 1451 00:50:21,000 --> 00:50:23,840 >> WELL, KNEW THANK YOU SO MUCH, 1452 00:50:23,840 --> 00:50:25,120 DR. CRISWELL, FOR THAT FANTASTIC 1453 00:50:25,120 --> 00:50:26,200 PRESENTATION, AND AGAIN, THANK 1454 00:50:26,200 --> 00:50:29,920 YOU, JENNIFER, FOR BEING WILLING 1455 00:50:29,920 --> 00:50:31,120 TO TELL US A LITTLE BIT ABOUT 1456 00:50:31,120 --> 00:50:32,600 WHAT IT'S LIKE TO HAVE LUPUS. 1457 00:50:32,600 --> 00:50:34,040 SO AT THIS POINT, WE'LL TURN 1458 00:50:34,040 --> 00:50:36,440 THINGS OVER TO OUR SECOND 1459 00:50:36,440 --> 00:50:38,160 SPEAKER, DR. HOLLAND. 1460 00:50:38,160 --> 00:50:45,240 STEVE, TAKE IT AWAY. 1461 00:50:45,240 --> 00:50:45,640 >> ALL RIGHT. 1462 00:50:45,640 --> 00:50:47,280 THANK YOU VERY MUCH, DAN, 1463 00:50:47,280 --> 00:50:47,840 LINDSEY AND JENNIFER. 1464 00:50:47,840 --> 00:50:49,720 THAT WAS REALLY AN EXTRAORDINARY 1465 00:50:49,720 --> 00:50:52,240 STORY, BOTH FROM THE PATIENT 1466 00:50:52,240 --> 00:50:53,320 STANDPOINT AND FROM THE 1467 00:50:53,320 --> 00:50:53,680 SCIENTIFIC ONE. 1468 00:50:53,680 --> 00:50:54,680 AND I HOPE THAT THE STORY I'M 1469 00:50:54,680 --> 00:50:57,040 GOING TO SHARE WITH YOU TODAY IS 1470 00:50:57,040 --> 00:50:58,640 A LITTLE BIT COMPLIMENTARY TO 1471 00:50:58,640 --> 00:51:01,600 THAT, AND THAT I'M LOOKING 1472 00:51:01,600 --> 00:51:03,480 FORWARD TO GETTING FEEDBACK. 1473 00:51:03,480 --> 00:51:06,240 SO I WANT TO TALK A LITTLE BIT 1474 00:51:06,240 --> 00:51:06,840 ABOUT ANTICYTOKINE AUTO 1475 00:51:06,840 --> 00:51:07,600 ANTIBODIES. 1476 00:51:07,600 --> 00:51:08,680 LET ME REMIND YOU AT THE 1477 00:51:08,680 --> 00:51:12,200 BEGINNING, CYTOKINES, THOSE ARE 1478 00:51:12,200 --> 00:51:13,160 HOW CELLS TALK TO EACH OTHER. 1479 00:51:13,160 --> 00:51:15,040 WE USE DIRECT MESSAGING, TEXT, 1480 00:51:15,040 --> 00:51:16,360 BUT CELLS LIKE TO SEND OUT 1481 00:51:16,360 --> 00:51:19,400 PROTEINS THAT GO FROM ONE TO THE 1482 00:51:19,400 --> 00:51:20,720 OTHER AND BIND TO RECEPTORS, 1483 00:51:20,720 --> 00:51:23,720 THEN THEY TELL THAT CELL WHAT TO 1484 00:51:23,720 --> 00:51:23,920 DO. 1485 00:51:23,920 --> 00:51:25,040 THAT'S WHAT WE'RE GOING TO FOCUS 1486 00:51:25,040 --> 00:51:26,880 ON TODAY. 1487 00:51:26,880 --> 00:51:29,840 I HAVE NO DISCLOSURES AND MY 1488 00:51:29,840 --> 00:51:31,080 OBJECTIVE IS JUST THAT YOU COME 1489 00:51:31,080 --> 00:51:34,800 AWAY APPRECIATING THAT THIS IS 1490 00:51:34,800 --> 00:51:35,440 REALLY NIFTY. 1491 00:51:35,440 --> 00:51:37,000 SO LET'S JUST START OUT, THOUGH, 1492 00:51:37,000 --> 00:51:39,960 WITH JUST TRYING TO PUT US IN 1493 00:51:39,960 --> 00:51:42,040 CONTEXT. 1494 00:51:42,040 --> 00:51:44,440 SO THIS GRAPH LOOKS AT -- IT'S A 1495 00:51:44,440 --> 00:51:45,960 DPRAF OF HUMAN POPULATION. 1496 00:51:45,960 --> 00:51:47,280 YOU MIGHT BE WONDERING, WELL, 1497 00:51:47,280 --> 00:51:50,440 YOU KNOW, STEVE, HOW DO YOU KNOW 1498 00:51:50,440 --> 00:51:53,320 WHAT POPULATION LOOKED LIKE BACK 1499 00:51:53,320 --> 00:51:58,800 IN SOME OF THESE EARLIER 1500 00:51:58,800 --> 00:51:59,760 PERIODS, BACK IN HERE, AND 1501 00:51:59,760 --> 00:52:00,920 FRANKLY IT'S BECAUSE I ASKED DAN 1502 00:52:00,920 --> 00:52:02,840 AND HE WAS ABLE TO GIVE ME SOME 1503 00:52:02,840 --> 00:52:03,880 DIRECT INSIGHT. 1504 00:52:03,880 --> 00:52:06,040 BUT NOW THE QUESTION HERE IS, 1505 00:52:06,040 --> 00:52:10,000 WHAT IS THE ROLE OF ANTIBIOTICS? 1506 00:52:10,000 --> 00:52:11,880 THAT IS, WE THINK -- I'M AN 1507 00:52:11,880 --> 00:52:12,600 INFECTIOUS DISEASE GUY. 1508 00:52:12,600 --> 00:52:14,040 WE THINK ANTIBIOTICS ARE 1509 00:52:14,040 --> 00:52:14,280 IMPORTANT. 1510 00:52:14,280 --> 00:52:14,920 WHEN WERE THEY GIVEN? 1511 00:52:14,920 --> 00:52:16,200 IF I HAD YOU GUYS IN FRONT OF 1512 00:52:16,200 --> 00:52:19,680 ME, I WOULD ASK YOU WHICH IS THE 1513 00:52:19,680 --> 00:52:21,680 FIRST ANTIBIOTIC, AND THE VAST 1514 00:52:21,680 --> 00:52:25,200 MAJORITY OF YOU WHO HAVE BEEN 1515 00:52:25,200 --> 00:52:27,840 MARKETED MERCILESSLY WOULD SAY, 1516 00:52:27,840 --> 00:52:28,840 OH, IT'S PENICILLIN. 1517 00:52:28,840 --> 00:52:30,800 NO, IT'S NOT PENICILLIN. 1518 00:52:30,800 --> 00:52:31,960 THE VER FIRST ANTIBIOTIC IN A 1519 00:52:31,960 --> 00:52:34,040 CENTENNIAL THAT WENT WITHOUT 1520 00:52:34,040 --> 00:52:35,560 APPROPRIATE HERALD WAS REALLY 1521 00:52:35,560 --> 00:52:42,160 MADE IN 1909, AND IT WAS CALLED 1522 00:52:42,160 --> 00:52:44,080 SALVORSAN, DEVELOPED FOR THE 1523 00:52:44,080 --> 00:52:45,120 TREATMENT OF AFRICAN SLEEPING 1524 00:52:45,120 --> 00:52:45,920 SICKNESS. 1525 00:52:45,920 --> 00:52:46,960 UNFORTUNATELY, IT REALLY WAS NOT 1526 00:52:46,960 --> 00:52:48,320 VERY ACTIVE AGAINST THAT, AND IT 1527 00:52:48,320 --> 00:52:49,880 WOUND UP BEING USED AGAINST 1528 00:52:49,880 --> 00:52:51,240 ANOTHER SLEEPING SICKNESS KNOWN 1529 00:52:51,240 --> 00:52:55,200 AS SYPHILIS. 1530 00:52:55,200 --> 00:53:00,560 BUT IT TOOK 33 YEARS FROM THE 1531 00:53:00,560 --> 00:53:03,080 DEVELOPMENT OF SALVORSAN TO THE 1532 00:53:03,080 --> 00:53:04,600 DEVELOPMENT OF PENICILLIN, AND 1533 00:53:04,600 --> 00:53:07,080 ALONG THE WAY WERE THE SULFA 1534 00:53:07,080 --> 00:53:07,280 DRUGS. 1535 00:53:07,280 --> 00:53:09,240 I WANT TO EMPHASIZE THAT DESPITE 1536 00:53:09,240 --> 00:53:10,520 THE FACT THAT ANTIBIOTIC 1537 00:53:10,520 --> 00:53:12,720 DEVELOPMENT HAS ONLY BEEN AROUND 1538 00:53:12,720 --> 00:53:14,240 FOR 100 YEARS, OUR SPECIES HAS 1539 00:53:14,240 --> 00:53:17,440 BEEN GROWING IN NUMBER. 1540 00:53:17,440 --> 00:53:18,480 AND I THINK THAT TELLS YOU THAT 1541 00:53:18,480 --> 00:53:20,000 WE ARE ACTUALLY BUILT TO GO THE 1542 00:53:20,000 --> 00:53:22,960 DISTANCE, AND SO WHEN WE DON'T, 1543 00:53:22,960 --> 00:53:24,240 WE WANT TO WONDER WHY. 1544 00:53:24,240 --> 00:53:25,560 FOR THOSE OF YOU THAT ARE 1545 00:53:25,560 --> 00:53:26,720 INTERESTED, I GET NOTHING FOR 1546 00:53:26,720 --> 00:53:28,440 TELLING YOU BUT THIS IS A 1547 00:53:28,440 --> 00:53:30,040 FANTASTIC BOOK, THE DEMON UNDER 1548 00:53:30,040 --> 00:53:31,240 THE MICROSCOPE, AND I CAN'T SAY 1549 00:53:31,240 --> 00:53:32,320 ENOUGH GOOD THINGS ABOUT IT. 1550 00:53:32,320 --> 00:53:34,360 ABOUT THE DEVELOPMENT OF 1551 00:53:34,360 --> 00:53:35,960 ANTIBIOTICS AND HOW 1552 00:53:35,960 --> 00:53:36,640 EXTRAORDINARY IT WAS. 1553 00:53:36,640 --> 00:53:37,720 BUT LOOK, THE REAL QUESTION 1554 00:53:37,720 --> 00:53:39,400 HERE, THE EL VANT IN THE ROOM, 1555 00:53:39,400 --> 00:53:41,840 IF YOU WILL, IS WHY DO PEOPLE 1556 00:53:41,840 --> 00:53:42,440 GET SICK? 1557 00:53:42,440 --> 00:53:43,560 THAT'S REALLY WHAT WE WANT TO 1558 00:53:43,560 --> 00:53:44,200 KNOW. 1559 00:53:44,200 --> 00:53:47,000 WHETHER WE'RE DOCTORS, PATIENTS, 1560 00:53:47,000 --> 00:53:48,640 OR INVESTORS, WE WANT TO KNOW 1561 00:53:48,640 --> 00:53:49,960 WHY ARE PEOPLE GETTING SICK? 1562 00:53:49,960 --> 00:53:51,200 BECAUSE WE WEREN'T BUILT IN 1563 00:53:51,200 --> 00:53:56,160 ORDER TO GET SICK. 1564 00:53:56,160 --> 00:53:57,880 SO THE LENS I USE FOR THIS ARE 1565 00:53:57,880 --> 00:53:59,000 CALLED PRIMARY IMMUNE 1566 00:53:59,000 --> 00:53:59,440 DEFICIENCIES. 1567 00:53:59,440 --> 00:54:00,080 WHAT ARE THOSE? 1568 00:54:00,080 --> 00:54:01,480 SO THEY GO BY SEVERAL DIFFERENT 1569 00:54:01,480 --> 00:54:01,800 NAMES. 1570 00:54:01,800 --> 00:54:04,520 OF COURSE JUST TO KEEP EVERYBODY 1571 00:54:04,520 --> 00:54:06,040 GUESSING, INBORN ERRORS OF 1572 00:54:06,040 --> 00:54:07,560 IMMUNITY, THAT IS HOW DO WE 1573 00:54:07,560 --> 00:54:10,880 PROTECT OURSELVES FROM 1574 00:54:10,880 --> 00:54:12,040 INFECTION, SOMETIMES REFERRED TO 1575 00:54:12,040 --> 00:54:13,800 AS CONGENITAL 1576 00:54:13,800 --> 00:54:14,400 IMMUNODEFICIENCIES, BUT THE 1577 00:54:14,400 --> 00:54:16,000 POINT IS THESE ARE 1578 00:54:16,000 --> 00:54:18,240 IMMUNODEFICIENCIES THAT ARE NOT 1579 00:54:18,240 --> 00:54:20,040 DUE TO THERAPY FOR LUPUS OR 1580 00:54:20,040 --> 00:54:21,520 THERAPY FOR CANCER. 1581 00:54:21,520 --> 00:54:23,200 THEY'RE NOT DUE TO HIV. 1582 00:54:23,200 --> 00:54:24,920 THEY'RE NOT DUE TO HAVING GOTTEN 1583 00:54:24,920 --> 00:54:25,760 A TRANSPLANT. 1584 00:54:25,760 --> 00:54:27,160 THESE ARE THINGS THAT YOU WERE 1585 00:54:27,160 --> 00:54:30,400 BORN WITH. 1586 00:54:30,400 --> 00:54:31,840 AND THE STUDY OF THESE OVER THE 1587 00:54:31,840 --> 00:54:35,760 LAST SEVERAL DECADES HAS REALLY 1588 00:54:35,760 --> 00:54:36,040 EXPLODED. 1589 00:54:36,040 --> 00:54:37,640 YOU CAN SEE HERE THE RATE OF THE 1590 00:54:37,640 --> 00:54:40,040 INCREASE OF THE NUMBER OF 1591 00:54:40,040 --> 00:54:41,600 RECOGNIZED PRIMARY IMMUNE 1592 00:54:41,600 --> 00:54:42,440 DEFICIENCIES, AND YOU SEE THAT 1593 00:54:42,440 --> 00:54:45,920 THE RATE HAS GONE UP REALLY 1594 00:54:45,920 --> 00:54:47,760 DRAMATICALLY, WHY IS THAT? 1595 00:54:47,760 --> 00:54:50,400 WELL, PARTLY BECAUSE WE KNOW A 1596 00:54:50,400 --> 00:54:50,840 LOT MORE. 1597 00:54:50,840 --> 00:54:52,120 YOU'RE HERE, YOU'RE PAYING 1598 00:54:52,120 --> 00:54:55,280 ATTENTION, MAYBE. 1599 00:54:55,280 --> 00:54:56,240 BUT THERE'S ALSO BETTER 1600 00:54:56,240 --> 00:54:57,440 SEQUENCING AND THE ABILITY TO 1601 00:54:57,440 --> 00:55:00,720 SEQUENCE THE DNA, IT HAS REALLY 1602 00:55:00,720 --> 00:55:01,800 TRANSFORMED HOW WE THINK ABOUT 1603 00:55:01,800 --> 00:55:02,640 DISEASE. 1604 00:55:02,640 --> 00:55:03,840 LINDSEY JUST TOLD YOU ABOUT NOT 1605 00:55:03,840 --> 00:55:05,600 ONLY SEQUENCING DNA, BUT LACKING 1606 00:55:05,600 --> 00:55:07,960 THEN AT LOOKING 1607 00:55:07,960 --> 00:55:09,440 AT WHAT BINDS TO THE DNA. 1608 00:55:09,440 --> 00:55:10,440 THESE ARE EXTRAORDINARY 1609 00:55:10,440 --> 00:55:11,080 OPPORTUNITIES. 1610 00:55:11,080 --> 00:55:12,120 WE'RE DOING MUCH BETTER TREATING 1611 00:55:12,120 --> 00:55:12,800 PATIENTS. 1612 00:55:12,800 --> 00:55:13,240 THEY SURVIVE. 1613 00:55:13,240 --> 00:55:18,960 WE HAVE A CLANS TO FIGURE OUT 1614 00:55:18,960 --> 00:55:19,880 PROBLEMS, AND THEN WE HAVE A 1615 00:55:19,880 --> 00:55:21,120 CHANCE TO DISSEMINATE 1616 00:55:21,120 --> 00:55:21,640 INFORMATION. 1617 00:55:21,640 --> 00:55:22,720 I WANT TO POINT THIS OUT BECAUSE 1618 00:55:22,720 --> 00:55:24,400 IT'S REALLY CHANGED THE WORLD. 1619 00:55:24,400 --> 00:55:29,920 AND THAT IS, WHEN WE LOOK AT THE 1620 00:55:29,920 --> 00:55:31,800 PREVALENCE OF PRIMARY IMMUNE 1621 00:55:31,800 --> 00:55:32,440 DEFICIENCIES WORLDWIDE, WHAT YOU 1622 00:55:32,440 --> 00:55:33,840 SEE IS THAT THE RATE OF PRIMARY 1623 00:55:33,840 --> 00:55:36,280 IMMUNE DEFICIENCIES IN THE 1624 00:55:36,280 --> 00:55:37,920 UNITED STATES IS SOMEWHERE 1625 00:55:37,920 --> 00:55:44,320 BETWEEN 5 AND 10 PER 100,000. 1626 00:55:44,320 --> 00:55:45,640 THAT MAY SEEM LIKE A BIG OR 1627 00:55:45,640 --> 00:55:46,520 SMALL NUMBER DEPENDING ON WHO 1628 00:55:46,520 --> 00:55:47,640 YOU ARE AND WHERE YOU COME FROM, 1629 00:55:47,640 --> 00:55:49,240 BUT I WANT TO CONTRAST TO THE 1630 00:55:49,240 --> 00:55:53,240 CURRENT RATE OF MYCOBACTERIUM 1631 00:55:53,240 --> 00:55:55,480 TUBERCULOSIS INFECTION, T.B., 1632 00:55:55,480 --> 00:55:56,920 THE GREATEST KILLER POTENTIALLY 1633 00:55:56,920 --> 00:55:58,840 OF ALL TIME, AND NOW IMMUNE 1634 00:55:58,840 --> 00:56:00,840 DEFICIENCIES ARE TWO TO THREE 1635 00:56:00,840 --> 00:56:06,040 TIMES MORE COMMON IN THIS 1636 00:56:06,040 --> 00:56:07,160 COUNTRY THAN TUBERCULOSIS. 1637 00:56:07,160 --> 00:56:08,280 IF YOU'RE A DOCTOR, THINK ABOUT 1638 00:56:08,280 --> 00:56:09,880 THE LAST TIME YOU SCREENED FOR 1639 00:56:09,880 --> 00:56:11,080 T.B. VERSUS THE LAST TIME YOU 1640 00:56:11,080 --> 00:56:13,000 SCREENED FOR AN IMMUNE 1641 00:56:13,000 --> 00:56:14,440 DEFICIENCY. 1642 00:56:14,440 --> 00:56:15,840 THE FACT THAT THE RATES ARE HIGH 1643 00:56:15,840 --> 00:56:17,240 IN THE UNITED STATES, IT'S NOT 1644 00:56:17,240 --> 00:56:19,040 BECAUSE OUR GENETICS ARE THAT 1645 00:56:19,040 --> 00:56:22,120 DIFFERENT THAN MOST OTHER 1646 00:56:22,120 --> 00:56:24,440 PLACES. 1647 00:56:24,440 --> 00:56:25,280 THIS IS BECAUSE WE'RE LOOKING 1648 00:56:25,280 --> 00:56:27,600 AND OTHER PLACES HAVE NOT GOTTEN 1649 00:56:27,600 --> 00:56:29,120 AROUND TO IT YET, BUT THIS IS 1650 00:56:29,120 --> 00:56:30,360 WHAT WE OUGHT TO CONSIDER THE 1651 00:56:30,360 --> 00:56:31,440 RATE IS AND IT'S GOING TO BE 1652 00:56:31,440 --> 00:56:35,400 GOING HIGHER AS WE DO MORE DNA 1653 00:56:35,400 --> 00:56:38,680 SEQUENCING. 1654 00:56:38,680 --> 00:56:39,640 SO THAT'S THE BACKGROUND I WANT 1655 00:56:39,640 --> 00:56:40,760 TO START WITH AND WHY AM I 1656 00:56:40,760 --> 00:56:42,240 TELLING YOU THIS? 1657 00:56:42,240 --> 00:56:45,840 BECAUSE MY PATIENT IS THIS 1658 00:56:45,840 --> 00:56:47,640 WOMAN. 1659 00:56:47,640 --> 00:56:49,000 WHO CAME HERE, WAS REFERRED TO 1660 00:56:49,000 --> 00:56:50,240 THE NIH BECAUSE SHE WAS 1661 00:56:50,240 --> 00:56:50,640 DESPERATELY ILL. 1662 00:56:50,640 --> 00:56:52,600 SHE WAS AT THAT POINT A 1663 00:56:52,600 --> 00:56:54,360 60-YEAR-OLD WHO HAD GROWN UP IN 1664 00:56:54,360 --> 00:56:56,320 VIETNAM, HAD SURVIVED THE WAR, 1665 00:56:56,320 --> 00:56:58,480 HAD COME OUT ON THE BOATS, HAD 1666 00:56:58,480 --> 00:57:00,560 LIVED THROUGH REFUGEE CAMPS, HAD 1667 00:57:00,560 --> 00:57:01,640 COME TO THE UNITED STATES WHERE 1668 00:57:01,640 --> 00:57:07,440 SHE ESTABLISHED A BUSINESS AND A 1669 00:57:07,440 --> 00:57:08,920 FAMILY AND WAS DOING GREAT UNTIL 1670 00:57:08,920 --> 00:57:11,400 SHE GOT INTO HER LATE LATE '50S AND 1671 00:57:11,400 --> 00:57:12,960 THEN REALLY STARTED TO LOSE 1672 00:57:12,960 --> 00:57:14,200 WEIGHT, HAD FEVERS, EVENTUALLY 1673 00:57:14,200 --> 00:57:14,920 WENT TO HER DOCTOR. 1674 00:57:14,920 --> 00:57:16,640 WHAT YOU SEE HERE ARE THESE 1675 00:57:16,640 --> 00:57:17,800 SPOTS ON HER CHEST. 1676 00:57:17,800 --> 00:57:21,400 AND THOSE SPOTS ARE TEEMING WITH 1677 00:57:21,400 --> 00:57:21,840 MYCOBACTERIA. 1678 00:57:21,840 --> 00:57:23,760 I'LL TELL YOU THAT IN A SECOND. 1679 00:57:23,760 --> 00:57:25,640 AND THEY'RE TEEMING WITH 1680 00:57:25,640 --> 00:57:26,520 MYCOBACTERIA BECAUSE SHE HAS 1681 00:57:26,520 --> 00:57:27,680 THESE INFECTIONS IN HER BONE 1682 00:57:27,680 --> 00:57:31,640 THAT ARE NOT ONLY DESTROYING THE 1683 00:57:31,640 --> 00:57:32,840 BONE, BUT THEY'RE THEN DRIVING 1684 00:57:32,840 --> 00:57:37,360 THEMSELVES OUT THROUGH THE SKIN. 1685 00:57:37,360 --> 00:57:38,760 AND PEOPLE SAID, WOW, THIS IS 1686 00:57:38,760 --> 00:57:42,360 BAD, AND WE DON'T KNOW WHY. 1687 00:57:42,360 --> 00:57:46,120 WHEN WE MET HER, WE SAID THIS IS 1688 00:57:46,120 --> 00:57:47,720 BAD, AND WE DON'T KNOW WHY. 1689 00:57:47,720 --> 00:57:49,920 SO WHAT ARE THESE MYCOBACTERIA? 1690 00:57:49,920 --> 00:57:52,320 IT WAS ALMOST 140 YEARS AGO THAT 1691 00:57:52,320 --> 00:57:55,200 ROBERT KOCH INVITED HIS FRIENDS 1692 00:57:55,200 --> 00:57:59,120 INTO HIS KITCHEN TO SHOW THEM 1693 00:57:59,120 --> 00:58:00,040 UNDER THE MICROSCOPE -- HE 1694 00:58:00,040 --> 00:58:01,520 INVITED THEM OVER FOR DINNER, 1695 00:58:01,520 --> 00:58:02,920 SHOW THEM UNDER THE MICROSCOPE 1696 00:58:02,920 --> 00:58:04,640 THE ORGANISM THAT HE THOUGHT 1697 00:58:04,640 --> 00:58:08,120 CAUSED TUBERCULOSIS. 1698 00:58:08,120 --> 00:58:09,080 WELL, OF COURSE ALL OF HIS 1699 00:58:09,080 --> 00:58:10,040 FRIENDS SAID ARE YOU CRAZY? 1700 00:58:10,040 --> 00:58:11,040 THAT'S WHY HE HAD TO COME UP 1701 00:58:11,040 --> 00:58:12,160 WITH THESE THINGS THAT 1702 00:58:12,160 --> 00:58:14,720 EVENTUALLY GOT CALLED KOCH'S 1703 00:58:14,720 --> 00:58:15,240 POSTULATES. 1704 00:58:15,240 --> 00:58:16,360 HOW DO YOU PROVE THAT WHAT YOU 1705 00:58:16,360 --> 00:58:20,240 THINK IS TRUE IS REALLY TRUE? 1706 00:58:20,240 --> 00:58:21,200 MORE IMPORTANT THAN THAT, 1707 00:58:21,200 --> 00:58:22,760 EVERYBODY SAID NO WAY WE'RE 1708 00:58:22,760 --> 00:58:24,040 HAVING DINNER AT BOB'S EVER 1709 00:58:24,040 --> 00:58:24,680 AGAIN. 1710 00:58:24,680 --> 00:58:27,720 WELL, OVER THE 140 YEARS SINCE 1711 00:58:27,720 --> 00:58:29,680 HE DISCOVERED THAT, WE'RE STILL 1712 00:58:29,680 --> 00:58:33,200 HAVING TROUBLE UNDERSTANDING WHY 1713 00:58:33,200 --> 00:58:33,880 PEOPLE GET TUBERCULOSIS. 1714 00:58:33,880 --> 00:58:37,000 THIS IS WHAT IT LOOKS LIKE UNDER 1715 00:58:37,000 --> 00:58:38,040 THE MICROSCOPE, AND THIS 1716 00:58:38,040 --> 00:58:39,360 CHARACTERISTIC SORT OF 1717 00:58:39,360 --> 00:58:42,280 RED-APPEARING BACTERIA IS REALLY 1718 00:58:42,280 --> 00:58:43,000 WHAT WE'RE AFTER. 1719 00:58:43,000 --> 00:58:45,360 WELL, IT TURNS OUT THAT M 1720 00:58:45,360 --> 00:58:46,240 TUBERCULOSIS IS AT THE VERY TOP 1721 00:58:46,240 --> 00:58:49,120 OF THAT PYRAMID OF PATHOGENESIS 1722 00:58:49,120 --> 00:58:50,640 OR VIRULENCE, IT'S A REALLY 1723 00:58:50,640 --> 00:58:51,800 NASTY BUG WHICH IS WHY EVERYBODY 1724 00:58:51,800 --> 00:58:52,640 KNOWS ABOUT IT. 1725 00:58:52,640 --> 00:58:56,920 AND THEN THERE ARE HUNDREDS MORE 1726 00:58:56,920 --> 00:58:57,440 MYCOBACTERIA. 1727 00:58:57,440 --> 00:59:02,600 AND YOU SEE HERE, I HAVE MADE A 1728 00:59:02,600 --> 00:59:05,200 FANCIFUL PYRAMID OF THE 1729 00:59:05,200 --> 00:59:05,800 NON-TUBERCULOUS MYCOBACTERIA, 1730 00:59:05,800 --> 00:59:07,600 BRILLIANT NAME, IT'S NOT 1731 00:59:07,600 --> 00:59:09,600 TUBERCULOSIS, THEREFORE IT'S A 1732 00:59:09,600 --> 00:59:10,200 NON-TUBERCULOUS MYCOBACTERIA. 1733 00:59:10,200 --> 00:59:11,320 I CAN'T TELL YOU WHERE THESE 1734 00:59:11,320 --> 00:59:11,920 NAMES COME FROM. 1735 00:59:11,920 --> 00:59:14,040 BUT THE NON-TUBERCULOUS 1736 00:59:14,040 --> 00:59:15,400 MYCOBACTERIA FOR THE MOST PART 1737 00:59:15,400 --> 00:59:16,360 DO NOT CAUSE SEVERE DISEASE. 1738 00:59:16,360 --> 00:59:20,160 IN FACT, THEY ONLY CAUSE SEVERE 1739 00:59:20,160 --> 00:59:22,680 DISEASE IN PEOPLE WHO HAVE MAJOR 1740 00:59:22,680 --> 00:59:24,560 SUSCEPTIBILITY FACTORS. 1741 00:59:24,560 --> 00:59:31,720 THOSE INBORN ERRORS OF IMMUNITY. 1742 00:59:31,720 --> 00:59:32,760 AND SO WHAT DO WE KNOW ABOUT 1743 00:59:32,760 --> 00:59:33,160 THESE? 1744 00:59:33,160 --> 00:59:36,640 SO WHAT WE KNOW IS THAT THE 1745 00:59:36,640 --> 00:59:38,640 ABILITY OF CELLS TO CONTROL 1746 00:59:38,640 --> 00:59:40,080 MYCOBACTERIA, AND JUST TO REMIND 1747 00:59:40,080 --> 00:59:43,800 YOU, ALMOST ALL OF THESE 1748 00:59:43,800 --> 00:59:45,680 ORGANISMS HERE ARE OUT IN THE 1749 00:59:45,680 --> 00:59:46,000 ENVIRONMENT. 1750 00:59:46,000 --> 00:59:48,840 M TUBERCULOSIS, THAT GETS SPREAD 1751 00:59:48,840 --> 00:59:49,960 MOSTLY HUMAN TO HUMAN. 1752 00:59:49,960 --> 00:59:51,160 THESE ORGANISMS ARE IN THE 1753 00:59:51,160 --> 00:59:54,800 ENVIRONMENT, AND YOU, I, 1754 00:59:54,800 --> 00:59:55,840 EVERYBODY GETS EXPOSED TO THEM 1755 00:59:55,840 --> 00:59:56,640 ALL THE TIME. 1756 00:59:56,640 --> 00:59:58,400 SO IF YOU'RE EXPOSED ALL THE 1757 00:59:58,400 --> 00:59:59,920 TIME, YOU BETTER HAVE A SYSTEM 1758 00:59:59,920 --> 01:00:01,240 IN PLACE THAT CONTROLS THEM. 1759 01:00:01,240 --> 01:00:03,600 AND THE GOOD NEWS IS, YOU DO. 1760 01:00:03,600 --> 01:00:04,320 HERE'S HOW IT WORKS. 1761 01:00:04,320 --> 01:00:06,440 THIS IS CALLED THE MACROPHAGE, 1762 01:00:06,440 --> 01:00:10,040 THIS LARGE CELL MACRO, BIG, 1763 01:00:10,040 --> 01:00:13,360 PHAGE, EATER, THE BIG EEGHT EATING 1764 01:00:13,360 --> 01:00:15,760 CELL THAT GOBBLES UP THE 1765 01:00:15,760 --> 01:00:16,080 MYCOBACTERIA. 1766 01:00:16,080 --> 01:00:17,960 AFTER THEY'RE INGESTED, THE CELL 1767 01:00:17,960 --> 01:00:19,160 MAKES INTERLEUKIN 12 WHICH BINDS 1768 01:00:19,160 --> 01:00:22,440 TO ITS RECEPTOR ON T-CELLS AND K 1769 01:00:22,440 --> 01:00:23,760 CELLS, AND THAT LEADS TO THE 1770 01:00:23,760 --> 01:00:27,880 PRODUCTION OF INTERFERON GAMMA, 1771 01:00:27,880 --> 01:00:29,440 WHICH THEN WORKS ON ITS RECEPTOR 1772 01:00:29,440 --> 01:00:31,400 ON ALL NUCLEATED CELLS IN THE 1773 01:00:31,400 --> 01:00:33,800 BODY, AND WHEN IT BINDS ITS 1774 01:00:33,800 --> 01:00:35,240 RECEPTOR, IT DOES A VARIETY OF 1775 01:00:35,240 --> 01:00:35,760 THINGS. 1776 01:00:35,760 --> 01:00:38,640 IT INCREASES TUMOR NECROSIS 1777 01:00:38,640 --> 01:00:40,480 FACTOR, WHICH IS A CYTOKINE THAT 1778 01:00:40,480 --> 01:00:42,320 MAKES FOR FEVER AND WEIGHT LOSS, 1779 01:00:42,320 --> 01:00:43,520 AND IT ALSO SIGNALS THEN THROUGH 1780 01:00:43,520 --> 01:00:48,320 OTHER MOLECULES TO LEAD TO THE 1781 01:00:48,320 --> 01:00:50,200 KILLING OF MYCOBACTERIA INSIDE 1782 01:00:50,200 --> 01:00:51,080 THE CELL. 1783 01:00:51,080 --> 01:00:53,440 AND 140 YEARS AFTER ROBERT KOCH 1784 01:00:53,440 --> 01:00:56,640 HAS IDENTIFIED THIS, WE STILL 1785 01:00:56,640 --> 01:00:59,040 DON'T KNOW EXACTLY HOW THE 1786 01:00:59,040 --> 01:01:00,240 MYCOBACTERIA ARE KILLED. 1787 01:01:00,240 --> 01:01:01,800 WE JUST KNOW IF YOU CAN'T DO THE 1788 01:01:01,800 --> 01:01:02,520 INTERFERON SIGNAL, YOU'RE IN 1789 01:01:02,520 --> 01:01:02,840 TROUBLE. 1790 01:01:02,840 --> 01:01:05,440 AND HOW DO WE KNOW THAT, BECAUSE 1791 01:01:05,440 --> 01:01:08,440 MUTATIONS IN ANY OF THESE GENES 1792 01:01:08,440 --> 01:01:14,640 AND SOME MORE LEAD TO SEVERE 1793 01:01:14,640 --> 01:01:15,160 DISSEMINATED MYCOBACTERIAL 1794 01:01:15,160 --> 01:01:15,840 DISEASE. 1795 01:01:15,840 --> 01:01:17,200 THEREFORE, IT'S ONE MAJOR 1796 01:01:17,200 --> 01:01:18,320 PATHWAY THAT DRIVES FROM 1797 01:01:18,320 --> 01:01:20,200 INGESTION OF MYCOBACTERIA TO 1798 01:01:20,200 --> 01:01:21,840 PRODUCTION OF IL-12 TO 1799 01:01:21,840 --> 01:01:23,160 PRODUCTION OF INTERFERON TO 1800 01:01:23,160 --> 01:01:26,960 SIGNALING THROUGH THE INTERFERON 1801 01:01:26,960 --> 01:01:29,480 RECEPTOR TO KILLING, AND 1802 01:01:29,480 --> 01:01:30,440 INTERFERON DRIVES FOR THE 1803 01:01:30,440 --> 01:01:31,520 PRODUCTION OF IL-12 SOME MORE. 1804 01:01:31,520 --> 01:01:33,480 SO IT'S A NEAT SYSTEM THAT 1805 01:01:33,480 --> 01:01:34,640 INTEROPERATES THROUGH THE 1806 01:01:34,640 --> 01:01:37,440 PRODUCTION OF CYTOKINES AND 1807 01:01:37,440 --> 01:01:39,200 THEIR SENSING BY RECEPTORS TO 1808 01:01:39,200 --> 01:01:41,240 LEAD TO THE KILLING AND CONTROL 1809 01:01:41,240 --> 01:01:44,360 OF MYCOBACTERIA. 1810 01:01:44,360 --> 01:01:46,320 NOW, OF COURSE THAT'S THE 1811 01:01:46,320 --> 01:01:46,760 SIMPLIFIED STORY. 1812 01:01:46,760 --> 01:01:51,680 BUT THAT'S NOT THE WHOLE STORY. 1813 01:01:51,680 --> 01:01:53,680 AND IT TURNS OUT THIS VACUOLE, 1814 01:01:53,680 --> 01:01:54,640 THIS CONTAINER INSIDE THE 1815 01:01:54,640 --> 01:01:55,840 MACROPHAGE ISN'T JUST DESIGNED 1816 01:01:55,840 --> 01:01:58,040 FOR THE CONTROL OF MYCOBACTERIA. 1817 01:01:58,040 --> 01:02:00,840 LOTS OF THINGS LIVE IN THERE. 1818 01:02:00,840 --> 01:02:01,640 FUNGI, BACTERIA. 1819 01:02:01,640 --> 01:02:05,400 SO HERE THEY ARE, HERE ARE THE 1820 01:02:05,400 --> 01:02:08,040 NON-TUBERCULOUS MYCOBACTERIA, 1821 01:02:08,040 --> 01:02:10,960 INCLUDING THE COMPLEX MY PATIENT 1822 01:02:10,960 --> 01:02:12,600 HAD, BUT THERE ARE OTHER 1823 01:02:12,600 --> 01:02:13,640 MYCOBACTERIA HERE. 1824 01:02:13,640 --> 01:02:15,840 MTB AND THIS OTHER ONE CALLED 1825 01:02:15,840 --> 01:02:19,040 BCG, AS WELL AS OTHER BACK BACTERIA 1826 01:02:19,040 --> 01:02:21,160 AND SOME FUNGI AND SOME VIRUSES. 1827 01:02:21,160 --> 01:02:24,240 SO THIS PATHWAY TURNS OUT TO BE 1828 01:02:24,240 --> 01:02:26,280 REALLY IMPORTANT FOR HOW WE 1829 01:02:26,280 --> 01:02:29,360 INTERACT WITH THINGS IN THE 1830 01:02:29,360 --> 01:02:31,400 ENVIRONMENT. 1831 01:02:31,400 --> 01:02:35,000 NOW, THIS TURNS OUT TO BE A 1832 01:02:35,000 --> 01:02:37,000 PATHWAY THAT WHEN THERE ARE 1833 01:02:37,000 --> 01:02:39,760 MUTATIONS IN IT MOSTLY SHOWS UP 1834 01:02:39,760 --> 01:02:41,640 IN CHILDHOOD BECAUSE, FRANKLY, 1835 01:02:41,640 --> 01:02:42,640 CHILDREN GET EXPOSED TO THINGS 1836 01:02:42,640 --> 01:02:46,840 EARLY ON, AND IF YOU GET A MAJOR 1837 01:02:46,840 --> 01:02:48,400 BREACH IN HOST DEFENSE, THEN YOU 1838 01:02:48,400 --> 01:02:49,880 GET SICK WHEN YOU ENCOUNTER IT. 1839 01:02:49,880 --> 01:02:51,440 SO MOST OF THESE DEFECTS START 1840 01:02:51,440 --> 01:02:51,760 EARLY. 1841 01:02:51,760 --> 01:02:53,320 SO NOW LET'S GO BACK TO OUR 1842 01:02:53,320 --> 01:02:53,760 PATIENT. 1843 01:02:53,760 --> 01:02:55,240 BECAUSE NO MATTER HOW YOU SLICE 1844 01:02:55,240 --> 01:02:57,560 IT, I MEAN, FOR REAL, 60 AIN'T 1845 01:02:57,560 --> 01:02:58,640 YOUNG. 1846 01:02:58,640 --> 01:03:01,240 AND SHE WAS FINE UNTIL SHE GOT 1847 01:03:01,240 --> 01:03:03,480 TO THAT LEVEL. 1848 01:03:03,480 --> 01:03:05,040 SO IF MOST OF THOSE GENETIC 1849 01:03:05,040 --> 01:03:07,280 DEFECTS START IN CHILDHOOD, AND 1850 01:03:07,280 --> 01:03:13,120 SHE'S GETTING SICK IN ADULTHOOD, 1851 01:03:13,120 --> 01:03:13,840 WHAT'S THE PROBLEM? 1852 01:03:13,840 --> 01:03:15,400 SO WHEN SHE CAME HERE TO THE 1853 01:03:15,400 --> 01:03:16,640 NIH, WE SAT DOWN AND SCRATCHED 1854 01:03:16,640 --> 01:03:18,440 OUR HEADS AND SAID, WELL, DOES 1855 01:03:18,440 --> 01:03:20,080 SHE HAVE A PROBLEM IN ANY OF 1856 01:03:20,080 --> 01:03:23,640 THESE GENES THAT WE'VE 1857 01:03:23,640 --> 01:03:25,920 IDENTIFIED BEFORE? 1858 01:03:25,920 --> 01:03:26,480 NO. 1859 01:03:26,480 --> 01:03:27,960 SO OUR PROBLEM WAS WHAT SHE HAD 1860 01:03:27,960 --> 01:03:29,440 LOOKED LIKE A GENETIC DISEASE, 1861 01:03:29,440 --> 01:03:31,160 IT ACTED LIKE A GENETIC DISEASE, 1862 01:03:31,160 --> 01:03:32,440 NO MATTER HOW MUCH DRUG THEY 1863 01:03:32,440 --> 01:03:34,160 GAVE HER, THEY COULDN'T GET HER 1864 01:03:34,160 --> 01:03:37,880 INFECTION UNDER CONTROL, BUT 1865 01:03:37,880 --> 01:03:39,040 IT'S COMING ON LATE LIFE. 1866 01:03:39,040 --> 01:03:42,120 AND WHEN WE TOOK THE CELLS IN 1867 01:03:42,120 --> 01:03:43,520 HER BLOOD AND ASKED THEM TO DO 1868 01:03:43,520 --> 01:03:47,000 AK BA TICS IN THE 1869 01:03:47,000 --> 01:03:47,840 ACROBATICS IN THE LAB, THEY WERE 1870 01:03:47,840 --> 01:03:48,080 FINE. 1871 01:03:48,080 --> 01:03:49,640 SO WHAT COULD REALLY BE GOING ON 1872 01:03:49,640 --> 01:03:50,040 HERE? 1873 01:03:50,040 --> 01:03:55,880 AND TO CUT TO THE PUNCH LINE, 1874 01:03:55,880 --> 01:03:59,240 WHAT SHE HAS IS AN ANTICYTOKINE 1875 01:03:59,240 --> 01:03:59,840 ANTICYTOKINE AUTOANTIBODIES. 1876 01:03:59,840 --> 01:04:01,640 THIS ONE ACTUALLY DIRECTED 1877 01:04:01,640 --> 01:04:02,640 AGAINST INTERFERON GAMMA ITSELF. 1878 01:04:02,640 --> 01:04:06,200 AND THIS ANTIBODY IS BINDING 1879 01:04:06,200 --> 01:04:07,280 INTERFERON, COMPLETELY BLOCKING 1880 01:04:07,280 --> 01:04:09,160 ITS ABILITY TO INTERACT WITHITY 1881 01:04:09,160 --> 01:04:11,000 RECEPTOR, AND, THEREFORE, 1882 01:04:11,000 --> 01:04:13,960 MIMICKING COMPLETELY THE 1883 01:04:13,960 --> 01:04:15,360 ABILITY -- MIMICKING COMPLETELY 1884 01:04:15,360 --> 01:04:19,000 THE CONDITION OF HAVING 1885 01:04:19,000 --> 01:04:20,000 INVITATION IN THE INTERFERON 1886 01:04:20,000 --> 01:04:23,240 GAMMA RECEPTOR. 1887 01:04:23,240 --> 01:04:24,640 SO AS WE STARTED INVESTIGATING 1888 01:04:24,640 --> 01:04:29,880 THIS CONDITION, WE REALIZED THAT 1889 01:04:29,880 --> 01:04:30,640 IT WAS BEING IDENTIFIED. 1890 01:04:30,640 --> 01:04:32,080 SO SHE WAS FROM VIETNAM. 1891 01:04:32,080 --> 01:04:33,840 HERE IS A REPORT OF A 1892 01:04:33,840 --> 01:04:36,960 25-YEAR-OLD WOMAN FROM THAILAND 1893 01:04:36,960 --> 01:04:38,200 WHO WAS LIVING IN GERMANY WHO 1894 01:04:38,200 --> 01:04:40,000 GOT ANOTHER MYCOBACTERIUM AND 1895 01:04:40,000 --> 01:04:46,640 THEN ANOTHER BACTERIA AND DIED. 1896 01:04:46,640 --> 01:04:48,840 25-YEAR-OLD WOMAN, PREVIOUSLY 1897 01:04:48,840 --> 01:04:49,080 HEALTHY. 1898 01:04:49,080 --> 01:04:51,040 ANOTHER REPORT OF A 57-YEAR-OLD 1899 01:04:51,040 --> 01:04:53,880 MAN WHO HAD TUBERCULOSIS, 1900 01:04:53,880 --> 01:04:55,560 ANOTHER NON-TUBERCULOUS 1901 01:04:55,560 --> 01:04:58,120 ORGANISM, AS WELL AS SOME 1902 01:04:58,120 --> 01:04:59,000 AUTOIMMUNE PROBLEMS, AND HE 1903 01:04:59,000 --> 01:04:59,360 DIED. 1904 01:04:59,360 --> 01:04:59,880 PREVIOUSLY HEALTHY MAN. 1905 01:04:59,880 --> 01:05:04,120 AND THEN ALONG THE WAY, WE WERE 1906 01:05:04,120 --> 01:05:05,080 COLLECTING PATIENTS WHO HAD 1907 01:05:05,080 --> 01:05:06,200 EXACTLY THE SAME PROBLEM, AND 1908 01:05:06,200 --> 01:05:08,400 WHAT WE FOUND WERE SIX WOMEN, 1909 01:05:08,400 --> 01:05:09,840 ALL FROM SOUTHEAST ASIA, 1910 01:05:09,840 --> 01:05:12,040 INCLUDING THE PATIENT I SHOWED 1911 01:05:12,040 --> 01:05:15,520 YOU, WHO HAD DISSEMINATED 1912 01:05:15,520 --> 01:05:16,320 MYCOBACTERIAL DISEASE, ALL OF 1913 01:05:16,320 --> 01:05:23,800 WHICH WERE EXTREMELY SEVERE. 1914 01:05:23,800 --> 01:05:25,040 SO WE SAID WAIT A MINUTE, THESE 1915 01:05:25,040 --> 01:05:30,600 PEOPLE ALL HAD ANTIINTERFERON 1916 01:05:30,600 --> 01:05:31,800 GAMMA AUTO ANTIBODIES. 1917 01:05:31,800 --> 01:05:33,640 BUT THEY'RE ALL SOUTHEAST ASIANS 1918 01:05:33,640 --> 01:05:34,920 OUTSIDE OF SOUTHEAST ASIA. 1919 01:05:34,920 --> 01:05:37,520 AND THE ANTIBODY THERE IS WHAT'S 1920 01:05:37,520 --> 01:05:39,080 CALLED IGG, THE MOST COMMON OF 1921 01:05:39,080 --> 01:05:40,640 THE ANTIBODY CLASSES THAT 1922 01:05:40,640 --> 01:05:41,640 COMBINE TO THESE THINGS, AND 1923 01:05:41,640 --> 01:05:43,040 THEY HAD A VARIETY OF PROBLEMS 1924 01:05:43,040 --> 01:05:44,120 LIKE THE ONES I'VE SHOWN YOU. 1925 01:05:44,120 --> 01:05:47,560 THEY HAD LOTS OF INFECTIONS. 1926 01:05:47,560 --> 01:05:49,360 WE REFER TO OPPORTUNISTIC 1927 01:05:49,360 --> 01:05:50,120 INFECTIONS THE INFECTIONS YOU'RE 1928 01:05:50,120 --> 01:05:51,160 NOT SUPPOSED TO GET UNLESS 1929 01:05:51,160 --> 01:05:51,760 YOU'RE PRETTY SICK. 1930 01:05:51,760 --> 01:05:53,440 THAT IS, THINGS FROM THE 1931 01:05:53,440 --> 01:05:54,200 ENVIRONMENT AREN'T USUALLY 1932 01:05:54,200 --> 01:05:55,440 SUPPOSED TO BE CAUSING YOU 1933 01:05:55,440 --> 01:05:55,640 DISEASE. 1934 01:05:55,640 --> 01:05:59,840 SO THEY WERE SEVERE, 1935 01:05:59,840 --> 01:06:00,600 DISSEMINATED AND FATAL. 1936 01:06:00,600 --> 01:06:02,640 SO WE BEGAN TO WONDER IF THESE 1937 01:06:02,640 --> 01:06:04,640 ANTIBODIES ARE ASSOCIATED WITH 1938 01:06:04,640 --> 01:06:07,760 DISSEMINATED NON-TUBERCULOUS MY 1939 01:06:07,760 --> 01:06:08,280 COBACK 1940 01:06:08,280 --> 01:06:09,520 MYCOBACTERIAL INFECTIONS IN 1941 01:06:09,520 --> 01:06:10,840 SOUTHEAST ASIANS OUTSIDE OF 1942 01:06:10,840 --> 01:06:13,040 SOUTHEAST ASIA, WHAT'S GOING ON 1943 01:06:13,040 --> 01:06:21,120 IN SOUTHEAST ASIA? 1944 01:06:21,120 --> 01:06:23,000 SO I WAS LUCKY ENOUGH TO HAVE 1945 01:06:23,000 --> 01:06:24,680 READ AN ARTICLE BY A GIFTED 1946 01:06:24,680 --> 01:06:27,440 INVESTIGATOR FROM THAILAND, AND 1947 01:06:27,440 --> 01:06:30,600 SHE REPORTED 59 PATIENTS IN 1948 01:06:30,600 --> 01:06:33,080 THAILAND WHO HAD ALL OF THESE 1949 01:06:33,080 --> 01:06:34,640 OPPORTUNISTIC INFECTIONS. 1950 01:06:34,640 --> 01:06:40,120 BACTERIAL, FUNGAL, VIRAL, AND 1951 01:06:40,120 --> 01:06:41,040 MYCOBACTERIA, BUT NONE OF THEM 1952 01:06:41,040 --> 01:06:41,440 HAD HIV. 1953 01:06:41,440 --> 01:06:42,640 THAT IS, THEY LOOKED LIKE THEY 1954 01:06:42,640 --> 01:06:49,040 HAD SEVERE HIV DISEASE, BUT THEY 1955 01:06:49,040 --> 01:06:49,520 DIDN'T. 1956 01:06:49,520 --> 01:06:51,200 WE REALIZED WHEN WE PUT TWO AND 1957 01:06:51,200 --> 01:06:52,080 TWO TOGETHER THAT WE WERE 1958 01:06:52,080 --> 01:06:53,040 PROBABLY DEALING WITH THE SAME 1959 01:06:53,040 --> 01:06:56,320 THING. 1960 01:06:56,320 --> 01:06:57,640 SO WORKING WITH SARAH BROWN WHO 1961 01:06:57,640 --> 01:07:03,840 WAS THEN IN MY LAB AND PETER 1962 01:07:03,840 --> 01:07:07,120 BURBELO, WE PUT TOGETHER A TRIAL 1963 01:07:07,120 --> 01:07:11,440 TO GO TO THAILAND AND TIE TAIWAN TO 1964 01:07:11,440 --> 01:07:12,040 TRY AND FIGURE OUT WHAT WAS 1965 01:07:12,040 --> 01:07:12,480 GOING ON. 1966 01:07:12,480 --> 01:07:13,840 I'M JUST GOING TO IDENTIFY HERE 1967 01:07:13,840 --> 01:07:15,440 FOR A MOMENT, WHAT WERE THE 1968 01:07:15,440 --> 01:07:16,560 GROUPS OF INDIVIDUALS WE SOUGHT 1969 01:07:16,560 --> 01:07:17,040 OUT? 1970 01:07:17,040 --> 01:07:18,720 WE HAD PEOPLE WHO HAD 1971 01:07:18,720 --> 01:07:21,440 DISSEMINATED NON-TUBERCULOUS 1972 01:07:21,440 --> 01:07:23,240 DISEASE, PEOPLE WHO HAD OTHER 1973 01:07:23,240 --> 01:07:26,560 OPPORTUNISTIC INFECTIONS, 1974 01:07:26,560 --> 01:07:28,240 VIRUSES, FUNGI, OTHER BACTERIA, 1975 01:07:28,240 --> 01:07:29,520 OTHER OPPORTUNISTIC INFORECASTS 1976 01:07:29,520 --> 01:07:32,960 WITH OR WITHOUT NON-TUBERCULOUS 1977 01:07:32,960 --> 01:07:33,520 DISEASE. 1978 01:07:33,520 --> 01:07:34,200 AND THEN BECAUSE THIS QUESTION 1979 01:07:34,200 --> 01:07:35,720 ABOUT WE THINK THAT THESE 1980 01:07:35,720 --> 01:07:38,600 MYCOBACTERIA ARE ALL IN A 1981 01:07:38,600 --> 01:07:39,400 SPECTRUM, SO WHAT'S THE 1982 01:07:39,400 --> 01:07:41,240 RELATIONSHIP BETWEEN THE 1983 01:07:41,240 --> 01:07:43,160 NON-TUBERCULOUS MYCOBACTERIA AND 1984 01:07:43,160 --> 01:07:43,480 TUBERCULOSIS? 1985 01:07:43,480 --> 01:07:45,440 SO WE HAD PATIENTS WITH 1986 01:07:45,440 --> 01:07:47,280 DISSEMINATED TUBERCULOSIS AND 1987 01:07:47,280 --> 01:07:49,480 PULMONARY TUBERCULOSIS, AND THEN 1988 01:07:49,480 --> 01:07:51,120 PEOPLE WHO WILL WERE DONORS IN A 1989 01:07:51,120 --> 01:07:52,560 BLOOD BANK WHO I THINK, FOR OUR 1990 01:07:52,560 --> 01:07:56,240 PURPOSES, WE'RE GOING TO SAY ARE 1991 01:07:56,240 --> 01:07:56,440 NORMAL. 1992 01:07:56,440 --> 01:07:57,240 WE PUT TOGETHER THIS GROUP OF 1993 01:07:57,240 --> 01:08:00,040 INDIVIDUALS AND THEN WE DECIDED 1994 01:08:00,040 --> 01:08:03,840 TO MEASURE, ACTUALLY WE MEASURED 1995 01:08:03,840 --> 01:08:04,840 41 CYTOKINES AT THE TIME BECAUSE 1996 01:08:04,840 --> 01:08:06,600 PETER HAD A BRILLIANT ASSAY HE 1997 01:08:06,600 --> 01:08:08,080 DEVISED THAT LET US DO THAT ON 1998 01:08:08,080 --> 01:08:09,960 TINY VOLUMES OF PLASMA, BUT HERE 1999 01:08:09,960 --> 01:08:12,120 I'M ONLY SHOWING YOU THE RESULTS 2000 01:08:12,120 --> 01:08:13,560 FOR THE ANTIBODY AGAINST 2001 01:08:13,560 --> 01:08:16,200 INTERFERON GAMMA, BECAUSE THAT 2002 01:08:16,200 --> 01:08:17,440 TURNED OUT TO BE THE MOST 2003 01:08:17,440 --> 01:08:19,880 IMPORTANT OF THE ONES THAT WE 2004 01:08:19,880 --> 01:08:20,200 IDENTIFIED. 2005 01:08:20,200 --> 01:08:21,960 AND SO WHEN WE PUT THIS GROUP 2006 01:08:21,960 --> 01:08:23,720 TOGETHER, DISSEMINATED DISEASE 2007 01:08:23,720 --> 01:08:26,640 VERSUS EVERYTHING ELSE, WHAT WE 2008 01:08:26,640 --> 01:08:29,240 SAW WAS THAT THE PEOPLE WHO HAD 2009 01:08:29,240 --> 01:08:31,160 DISSEMINATED DISEASE WITH EITHER 2010 01:08:31,160 --> 01:08:32,480 NON-TUBERCULOUS OR OTHER 2011 01:08:32,480 --> 01:08:33,720 OPPORTUNISTIC INFECTIONS, THE 2012 01:08:33,720 --> 01:08:37,160 VAST MAJORITY OF THEM HAD 2013 01:08:37,160 --> 01:08:41,960 EXTRAORDINARILY HIGH LEVELS OF 2014 01:08:41,960 --> 01:08:43,240 ANTIBODIES AGAINST INTERFERON 2015 01:08:43,240 --> 01:08:44,320 GAMMA. 2016 01:08:44,320 --> 01:08:45,840 FASCINATINGLY, THOSE WHO HAD 2017 01:08:45,840 --> 01:08:47,120 TUBERCULOSIS EITHER DISSEMINATED 2018 01:08:47,120 --> 01:08:51,680 OR ISOLATED TO THE LUNG, THEY 2019 01:08:51,680 --> 01:08:53,760 DIDN'T. 2020 01:08:53,760 --> 01:08:54,640 SHOCKING. 2021 01:08:54,640 --> 01:08:55,240 ABSOLUTELY SHOCKING. 2022 01:08:55,240 --> 01:08:56,920 I'LL SAVE YOU ANY EFFORT NOW, I 2023 01:08:56,920 --> 01:08:57,360 DON'T KNOW WHY. 2024 01:08:57,360 --> 01:09:03,800 BUT I WOULD ARGUE THAT IT'S 2025 01:09:03,800 --> 01:09:05,880 BECAUSE TUBERCULOSIS AND THESE 2026 01:09:05,880 --> 01:09:06,800 NON-TUBERCULOUS ORGANISMS ARE 2027 01:09:06,800 --> 01:09:07,400 NOT THE SAME. 2028 01:09:07,400 --> 01:09:09,040 BUT IT WAS HIGHLY ASSOCIATED 2029 01:09:09,040 --> 01:09:12,680 WITH AN ANTIBODY AGAINST INFEAR 2030 01:09:12,680 --> 01:09:14,200 ON -- THAT WAS MIMICKING THE 2031 01:09:14,200 --> 01:09:15,440 PROBLEM WHEN YOU MUTE RECEPTORS. 2032 01:09:15,440 --> 01:09:16,360 WHAT DID IT LOOK LIKE? 2033 01:09:16,360 --> 01:09:17,440 THESE PEOPLE WERE REALLY, REALLY 2034 01:09:17,440 --> 01:09:17,800 SICK. 2035 01:09:17,800 --> 01:09:19,480 YOU CAN SEE THIS MAN HAD TWO 2036 01:09:19,480 --> 01:09:21,120 INFECTIONS GOING ON AT THE SAME 2037 01:09:21,120 --> 01:09:21,920 TIME. 2038 01:09:21,920 --> 01:09:23,480 A DISSEMINATED FUNGAL INFECTION 2039 01:09:23,480 --> 01:09:25,880 AND A DISSEMINATED MYCOBACTERIAL 2040 01:09:25,880 --> 01:09:26,600 INFECTION. 2041 01:09:26,600 --> 01:09:29,360 THIS WOMAN HAD HUGE LYMPH NODES 2042 01:09:29,360 --> 01:09:31,080 DUE TO SALMONELLA, WHICH IS A 2043 01:09:31,080 --> 01:09:32,080 BACTERIA. 2044 01:09:32,080 --> 01:09:34,200 HERE YOU CAN SEE THIS YOUNG MAN 2045 01:09:34,200 --> 01:09:39,720 HAD AN INFECTION IN HIS BONE 2046 01:09:39,720 --> 01:09:41,440 WITH CRYPTOCOCCUS, WHICH IS A 2047 01:09:41,440 --> 01:09:43,040 FUNGUS, AND THIS YOUNG WOMAN HAD 2048 01:09:43,040 --> 01:09:43,600 EXTENSIVE SKIN DISEASE. 2049 01:09:43,600 --> 01:09:46,640 SO ALL OF THESE IN PEOPLE WHO 2050 01:09:46,640 --> 01:09:48,760 HAD HIGH LEVELS OF ANTIBODY 2051 01:09:48,760 --> 01:09:56,080 AGAINST INTERFERON GAMMA. 2052 01:09:56,080 --> 01:09:57,200 THE FIRST POINT HERE IS THAT 2053 01:09:57,200 --> 01:09:58,560 THESE ANTIBODIES THAT COME ON 2054 01:09:58,560 --> 01:10:00,400 LATE IN LIFE MIMIC GENETIC DUS 2055 01:10:00,400 --> 01:10:01,840 ORDERS AND YOU CAN SEE, I THINK, 2056 01:10:01,840 --> 01:10:02,600 EXACTLY WHY. 2057 01:10:02,600 --> 01:10:05,440 THEY TAKE OUT A CRITICAL SIGNAL 2058 01:10:05,440 --> 01:10:07,400 MOLECULE THAT'S IN EXACTLY THE 2059 01:10:07,400 --> 01:10:08,600 SAME PATHWAY AS ALL THE OTHER 2060 01:10:08,600 --> 01:10:09,520 DEFECTS THAT HAD BEEN 2061 01:10:09,520 --> 01:10:12,840 IDENTIFIED. 2062 01:10:12,840 --> 01:10:18,920 SO THEN I THINK ALL OF US, AS 16 2063 01:10:18,920 --> 01:10:21,480 SHANT HUMANS, SPEND A LOT OF 2064 01:10:21,480 --> 01:10:23,640 TIME SAYING WHY, WHY ME, WHY 2065 01:10:23,640 --> 01:10:25,040 NOW, WHY THIS PROBLEM? 2066 01:10:25,040 --> 01:10:30,160 AND THAT WAS THE QUESTION THAT 2067 01:10:30,160 --> 01:10:31,320 PEOPLE TURNED TO NEXT. 2068 01:10:31,320 --> 01:10:33,560 SO WHY DID THESE PEOPLE START TO 2069 01:10:33,560 --> 01:10:36,920 GET THESE PROBLEMS, AND WHY WERE 2070 01:10:36,920 --> 01:10:38,080 WE FINDING IT SO FREQUENTLY IN 2071 01:10:38,080 --> 01:10:39,480 PEOPLE THAT ORIGINATED IN 2072 01:10:39,480 --> 01:10:44,480 SOUTHEAST ASIA, BUT NOT IN THE 2073 01:10:44,480 --> 01:10:45,680 VASTLY LARGER NUMBER OF PEOPLE 2074 01:10:45,680 --> 01:10:46,440 IN THE COUNTRIES THAT 2075 01:10:46,440 --> 01:10:49,440 SURROUNDING THEM. 2076 01:10:49,440 --> 01:10:53,040 SO A REALLY GIFTED GROUP IN 2077 01:10:53,040 --> 01:10:53,960 TAIWAN BEGAN TO LOOK INTO THIS 2078 01:10:53,960 --> 01:10:56,040 AND THEY FOCUSED ON THE HLA 2079 01:10:56,040 --> 01:10:56,320 MOLECULES. 2080 01:10:56,320 --> 01:10:57,360 NOW YOU MAY HAVE SEEN THAT 2081 01:10:57,360 --> 01:11:00,120 COMING UP IN LINDSEY'S DATA, 2082 01:11:00,120 --> 01:11:01,640 THAT BIG -- THE HIGHEST PEAK 2083 01:11:01,640 --> 01:11:04,680 THAT SHE HAD FOR MOST OF HER 2084 01:11:04,680 --> 01:11:07,040 GENOME-WIDE ASSOCIATIONS WAS IN 2085 01:11:07,040 --> 01:11:08,240 THE MHC COMPLEX. 2086 01:11:08,240 --> 01:11:10,760 AND SOME OF THOSE MHC MOLECULES, 2087 01:11:10,760 --> 01:11:12,240 THIS IS WHAT THEY DO. 2088 01:11:12,240 --> 01:11:14,200 THEY COME TOGETHER IN A LITTLE 2089 01:11:14,200 --> 01:11:16,400 CLUSTER, AND THEY FORM A VERY 2090 01:11:16,400 --> 01:11:19,200 SPECIAL POCKET, AND ONLY 2091 01:11:19,200 --> 01:11:21,840 SPECIFIC KEYS CAN FIT INTO THE 2092 01:11:21,840 --> 01:11:23,440 POCKET THAT THEY FORM. 2093 01:11:23,440 --> 01:11:25,840 AND WHAT THEY IDENTIFIED IN 2094 01:11:25,840 --> 01:11:28,480 PATIENTS WHO HAD THESE 2095 01:11:28,480 --> 01:11:30,240 ANTIINTERFERON AUTO ANTIBODIES, 2096 01:11:30,240 --> 01:11:31,760 WERE TWO PARTICULAR MOLECULES 2097 01:11:31,760 --> 01:11:34,400 THAT GO INTO MAKING UP THOSE 2098 01:11:34,400 --> 01:11:39,880 POCKETS OF THE HLA COMPLEX. 2099 01:11:39,880 --> 01:11:41,120 THAT WAS SORT OF FASCINATING IN 2100 01:11:41,120 --> 01:11:42,040 AND OF ITSELF. 2101 01:11:42,040 --> 01:11:46,560 THEY WENT ON TO SAY, OKAY, WHY 2102 01:11:46,560 --> 01:11:47,720 IS THAT PARTICULAR SET OF 2103 01:11:47,720 --> 01:11:48,840 MOLECULES OCCURRING? 2104 01:11:48,840 --> 01:11:50,040 REMEMBER, THOSE MOLECULES ARE 2105 01:11:50,040 --> 01:11:53,480 MAKING THE CAPACITY TO BIND ONLY 2106 01:11:53,480 --> 01:11:54,520 CERTAIN THINGS. 2107 01:11:54,520 --> 01:11:55,720 WELL, WHAT WAS THE CERTAIN THING 2108 01:11:55,720 --> 01:11:56,480 THEY BOUND? 2109 01:11:56,480 --> 01:11:59,040 IT TURNS OUT THAT THAT BINDING 2110 01:11:59,040 --> 01:12:02,240 POCKET MADE BY THOSE MOLECULES 2111 01:12:02,240 --> 01:12:05,720 CORRESPONDS TO THE LAST AMINO 2112 01:12:05,720 --> 01:12:07,080 ACIDS OF THE INTERFERON GAMMA 2113 01:12:07,080 --> 01:12:11,240 MOLECULE. 2114 01:12:11,240 --> 01:12:12,640 AND EVEN MORE INTERESTINGLY, 2115 01:12:12,640 --> 01:12:14,200 THAT LAST PART OF THE INTERFERON 2116 01:12:14,200 --> 01:12:18,280 GAMMA MOLECULE HERE SHOWN IN RED 2117 01:12:18,280 --> 01:12:23,240 TURNS OUT TO BE IDENTICAL TO 2118 01:12:23,240 --> 01:12:25,080 ANOTHER GENE THAT SHOWS UP IN A 2119 01:12:25,080 --> 01:12:27,240 FUNGUS CALLED ASPERGILLUS. 2120 01:12:27,240 --> 01:12:28,680 WELL, HERE YOU SEE IN THIS 2121 01:12:28,680 --> 01:12:30,440 TABLE, THIS IS THE AMINO ACID 2122 01:12:30,440 --> 01:12:33,520 SEQUENCE OF INTERFERON GAMMA. 2123 01:12:33,520 --> 01:12:35,560 THIS IS THE AMINO ACID SEQUENCE 2124 01:12:35,560 --> 01:12:41,920 OF THIS GENE CALLED NOC2 IN AS 2125 01:12:41,920 --> 01:12:43,040 PER JILL US. 2126 01:12:43,040 --> 01:12:44,640 THOSE AUTHORS SAID WAIT A 2127 01:12:44,640 --> 01:12:45,440 MINUTE, HERE'S WHAT WE THINK IS 2128 01:12:45,440 --> 01:12:48,320 GOING ON, WE THINK HUMANS ARE 2129 01:12:48,320 --> 01:12:50,440 INHALING, OR MAYBE EATING, 2130 01:12:50,440 --> 01:12:52,000 ASPERGILLUS, AND THAT THEY 2131 01:12:52,000 --> 01:12:54,560 THEN -- THEIR IMMUNE SYSTEM 2132 01:12:54,560 --> 01:12:56,640 RECOGNIZES THIS PROTEIN IN 2133 01:12:56,640 --> 01:12:58,520 ASPERGILLUS CALLED NOC2. 2134 01:12:58,520 --> 01:13:00,200 YOU THEN MAKE AN ANTIBODY 2135 01:13:00,200 --> 01:13:04,200 AGAINST THAT PROTEIN NOC2, BUT 2136 01:13:04,200 --> 01:13:07,080 THAT ANTIBODY AGAINST 2137 01:13:07,080 --> 01:13:07,800 NOC2 CROSS-REACTS AGAINST 2138 01:13:07,800 --> 01:13:09,400 INTERFERON GAMMA, AND NOW THAT 2139 01:13:09,400 --> 01:13:11,200 ANTIBODY IS BLOCKING THE 2140 01:13:11,200 --> 01:13:13,840 INTERFERON HERE IN THE GREEN, 2141 01:13:13,840 --> 01:13:17,880 AND THEN CAUSING THIS PROBLEM OF 2142 01:13:17,880 --> 01:13:20,880 INTERFERON GAMMA DEFICIENCY DUE 2143 01:13:20,880 --> 01:13:21,680 TO AN ANTIBODY. 2144 01:13:21,680 --> 01:13:23,480 AND THEY SHOW THAT THIS MADE 2145 01:13:23,480 --> 01:13:25,400 SOME SENSE BECAUSE THEY COULD 2146 01:13:25,400 --> 01:13:28,360 ACTUALLY TAKE THE MOLECULE 2147 01:13:28,360 --> 01:13:29,440 INTERFERON GAMMA TO TAKE OUT 2148 01:13:29,440 --> 01:13:30,720 THAT PART THAT WAS BEING 2149 01:13:30,720 --> 01:13:31,840 RECOGNIZED BY THE ANTIBODY AND 2150 01:13:31,840 --> 01:13:33,440 THEN THE INTERFERON WORKED ALL 2151 01:13:33,440 --> 01:13:34,040 OVER AGAIN. 2152 01:13:34,040 --> 01:13:35,480 SO HERE THEY'VE CHANGED IT FROM 2153 01:13:35,480 --> 01:13:39,600 A DIE MONDAY TO DIAMOND TO A TIER DROP. 2154 01:13:39,600 --> 01:13:42,680 WHETHER THIS IS EXACTLY THE 2155 01:13:42,680 --> 01:13:45,720 EXPOSURE THAT LEADS TO MOLECULAR 2156 01:13:45,720 --> 01:13:47,160 MIMIC RE, I DON'T KNOW, BUT IT 2157 01:13:47,160 --> 01:13:48,040 CERTAINLY MAKES SENSE AND IT'S 2158 01:13:48,040 --> 01:13:50,040 CLEAR THAT JUST AS LINDSEY WAS 2159 01:13:50,040 --> 01:13:51,240 TALKING ABOUT, ABOUT 2160 01:13:51,240 --> 01:13:53,640 ENVIRONMENTAL EXPOSURES, THIS IS 2161 01:13:53,640 --> 01:13:55,800 AN ENVIRONMENTAL EXPOSURE THAT 2162 01:13:55,800 --> 01:13:57,240 COULD BE DRIVING AN IMMUNE 2163 01:13:57,240 --> 01:13:58,640 REACTION THAT THEN LEADS TO 2164 01:13:58,640 --> 01:14:09,240 SEVERE DISEASE. 2165 01:14:09,240 --> 01:14:10,360 ONCE YOU UNDERSTAND THE DISEASE, 2166 01:14:10,360 --> 01:14:11,320 YOU CAN CHANGE ITS COURSE. 2167 01:14:11,320 --> 01:14:12,720 SO ONCE WE IDENTIFIED THAT THESE 2168 01:14:12,720 --> 01:14:13,480 PATIENTS WERE GETTING SICK 2169 01:14:13,480 --> 01:14:15,440 BECAUSE THEY HAD AUTO ANTIBODIES 2170 01:14:15,440 --> 01:14:16,720 AGAINST INTERFERON GAMMA, AND WE 2171 01:14:16,720 --> 01:14:18,480 KNOW THAT ANTIBODIES ARE MADE BY 2172 01:14:18,480 --> 01:14:20,360 B CELLS, THEN WE REALIZE THAT WE 2173 01:14:20,360 --> 01:14:22,640 COULD GO AND WHACK THOSE B CELLS 2174 01:14:22,640 --> 01:14:24,640 AND MAKE THEIR ANTIBODIES GO 2175 01:14:24,640 --> 01:14:26,120 DOWN. 2176 01:14:26,120 --> 01:14:29,160 SO IN FACT, HERE WAS THE LEVEL 2177 01:14:29,160 --> 01:14:30,320 OF ANTIBODY BEFORE TREATMENT, 2178 01:14:30,320 --> 01:14:31,640 AND HERE'S WHAT HAPPENS TO 2179 01:14:31,640 --> 01:14:34,840 ANTIBODY DURING TREATMENT, AND 2180 01:14:34,840 --> 01:14:36,480 THEN HERE'S WHAT HAPPENS AFTER 2181 01:14:36,480 --> 01:14:36,760 TREATMENT. 2182 01:14:36,760 --> 01:14:39,240 AS FURTHER PROOF THAT THIS IS 2183 01:14:39,240 --> 01:14:40,640 REALLY IMPORTANT, THIS IS THE 2184 01:14:40,640 --> 01:14:42,120 PATIENT WHOSE SLIDE I SHOWED 2185 01:14:42,120 --> 01:14:44,880 YOU, WHO HAD THE SPOTS ON HER 2186 01:14:44,880 --> 01:14:45,440 CHEST. 2187 01:14:45,440 --> 01:14:47,280 WHEN WE STOPPED GIVING HER THE 2188 01:14:47,280 --> 01:14:49,080 DRUG TO TAKE OUT THE B CELLS, 2189 01:14:49,080 --> 01:14:51,000 HER LEVELS WENT UP, SHE HAD A 2190 01:14:51,000 --> 01:14:53,240 CLINICAL RELAPSE, THAT IS, HER 2191 01:14:53,240 --> 01:14:54,240 INFECTIONS CAME BACK, AND WE HAD 2192 01:14:54,240 --> 01:14:56,880 TO GIVE TO HER AGAIN AND THEN 2193 01:14:56,880 --> 01:15:00,480 EVERYTHING RESOLVED AND WENT 2194 01:15:00,480 --> 01:15:02,760 AWAY. 2195 01:15:02,760 --> 01:15:04,760 SO THIS ARE A FASCINATING 2196 01:15:04,760 --> 01:15:08,160 EXAMPLE OF WHAT WE REFER TO AS 2197 01:15:08,160 --> 01:15:10,240 GENETICS, GENDER AND GEOGRAPHY. 2198 01:15:10,240 --> 01:15:11,040 GENETICS IS OBVIOUS BECAUSE 2199 01:15:11,040 --> 01:15:14,280 YOU'VE GOT THE HLA ASSOCIATION. 2200 01:15:14,280 --> 01:15:16,440 THE GENDER IS FAST FASCINATING 2201 01:15:16,440 --> 01:15:17,840 BECAUSE THE VAST MAJORITY OF 2202 01:15:17,840 --> 01:15:19,800 PEOPLE OUTSIDE OF SOUTHEAST ASIA 2203 01:15:19,800 --> 01:15:20,880 WHO HAVE BEEN IDENTIFIED ARE 2204 01:15:20,880 --> 01:15:24,120 WOMEN. 2205 01:15:24,120 --> 01:15:26,520 WHEREAS IN SOUTHEAST ASIA, THE 2206 01:15:26,520 --> 01:15:27,960 RATES BETWEEN MEN AND WOMEN ARE 2207 01:15:27,960 --> 01:15:28,840 GENERALLY THE SAME. 2208 01:15:28,840 --> 01:15:30,200 AND GEOGRAPHY, BECAUSE IT'S ONLY 2209 01:15:30,200 --> 01:15:31,480 PEOPLE WHO ARE BORN THERE IN 2210 01:15:31,480 --> 01:15:32,920 SOUTHEAST ASIA FOR MOST PART IN 2211 01:15:32,920 --> 01:15:35,640 WHOM THIS HAPPENS. 2212 01:15:35,640 --> 01:15:36,680 PEOPLE OF THE SAME ETHNICITY 2213 01:15:36,680 --> 01:15:38,880 BORN ELSEWHERE DON'T SEEM TO BE 2214 01:15:38,880 --> 01:15:40,600 AS SUSCEPTIBLE. 2215 01:15:40,600 --> 01:15:41,840 IT'S CLEARLY GOT GENETIC 2216 01:15:41,840 --> 01:15:42,920 COMPONENTS AND I THINK WE CAN 2217 01:15:42,920 --> 01:15:47,240 TREAT IT. 2218 01:15:47,240 --> 01:15:49,080 SO THAT'S AN EXAMPLE, ONLY ONE 2219 01:15:49,080 --> 01:15:52,840 EXAMPLE OF AN ANCYTOKINE AUTO 2220 01:15:52,840 --> 01:15:55,080 ANTIBODY CAUSING A DISEASE THAT 2221 01:15:55,080 --> 01:15:56,640 MIMICS A MENDELIAN DISEASE. 2222 01:15:56,640 --> 01:15:58,440 NOW THE NEXT QUESTION IS, WELL, 2223 01:15:58,440 --> 01:16:01,360 OKAY, THAT'S A RARE SET OF 2224 01:16:01,360 --> 01:16:01,640 PROBLEMS. 2225 01:16:01,640 --> 01:16:02,840 IS THIS INVOLVED IN COMMON 2226 01:16:02,840 --> 01:16:03,320 PROBLEMS? 2227 01:16:03,320 --> 01:16:06,400 DOES THIS OCCUR OUTSIDE OF THOSE 2228 01:16:06,400 --> 01:16:08,000 PRIMARY IMMUNE DEFICIENCY-LIKE 2229 01:16:08,000 --> 01:16:08,560 DISEASES? 2230 01:16:08,560 --> 01:16:09,880 DO THESE OCCUR IN MORE COMMON 2231 01:16:09,880 --> 01:16:11,800 DISEASES? 2232 01:16:11,800 --> 01:16:13,480 SO HARKING BACK TO WHAT LINDSEY 2233 01:16:13,480 --> 01:16:20,240 WAS TALKING ABOUT, WE WORKED 2234 01:16:20,240 --> 01:16:28,320 WITH SARTHAK GUPTA AND HARRY 2235 01:16:28,320 --> 01:16:31,200 MOTSOUPOULOS TO SAY OKAY, WHAT 2236 01:16:31,200 --> 01:16:33,080 ABOUT THE -- ARE THESE AUTO 2237 01:16:33,080 --> 01:16:34,560 BODIES OCCURRING THERE AND IF 2238 01:16:34,560 --> 01:16:35,440 SO, ARE THEY IMPORTANT? 2239 01:16:35,440 --> 01:16:37,080 SO JUST REMIND YOU THAT LUPUS 2240 01:16:37,080 --> 01:16:38,400 OCCURS IN ABOUT ONE-TENTH OF 1% 2241 01:16:38,400 --> 01:16:39,560 OF THE POPULATION. 2242 01:16:39,560 --> 01:16:41,080 BUT THAT'S A BIG NUMBER WHEN 2243 01:16:41,080 --> 01:16:44,280 YOU'RE TALKING ABOUT 330 MILLION 2244 01:16:44,280 --> 01:16:45,000 PEOPLE. 2245 01:16:45,000 --> 01:16:47,280 RHEUMATOID ARTHRITIS, ABOUT 1%, 2246 01:16:47,280 --> 01:16:51,480 AND SLOW SJOGREN'S, UP TO 3% OF THE 2247 01:16:51,480 --> 01:16:52,200 U.S. POPULATION. 2248 01:16:52,200 --> 01:16:54,160 SO THESE ARE BIG TIME DISEASES. 2249 01:16:54,160 --> 01:16:56,280 AND WE PERFORMED A SIMILAR 2250 01:16:56,280 --> 01:16:56,600 EXPLORATION. 2251 01:16:56,600 --> 01:17:00,640 TRYING TO IDENTIFY ANTIBODIES 2252 01:17:00,640 --> 01:17:01,600 AGAINST CYTOKINES IN PATIENTS 2253 01:17:01,600 --> 01:17:03,840 WHO HAD THOSE DISEASES. 2254 01:17:03,840 --> 01:17:04,680 SO WHAT DID WE FIND? 2255 01:17:04,680 --> 01:17:06,000 AND I'M JUST GOING TO BRIEFLY 2256 01:17:06,000 --> 01:17:09,120 HIGHLIGHT THIS. 2257 01:17:09,120 --> 01:17:10,360 WE FOUND ACTUALLY THERE WERE A 2258 01:17:10,360 --> 01:17:12,000 FAIR NUMBER OF ANTIBODIES 2259 01:17:12,000 --> 01:17:13,840 AGAINST INTERFERONS AND OTHER 2260 01:17:13,840 --> 01:17:17,360 CYTOKINES IN THIS POPULATION. 2261 01:17:17,360 --> 01:17:21,080 SO HOOR THE BLACK HERE THE BLACK BOXES AR E THE 2262 01:17:21,080 --> 01:17:22,560 NORMAL RANGE IDENTIFIED THROUGH 2263 01:17:22,560 --> 01:17:23,920 ESSENTIALLY NORMAL VOLUNTEERS OR 2264 01:17:23,920 --> 01:17:25,800 BLOOD BANK CONTROL, AND ANYTHING 2265 01:17:25,800 --> 01:17:30,520 OUTSIDE OF THOSE BLACK BARS IS 2266 01:17:30,520 --> 01:17:30,960 ELEVATED. 2267 01:17:30,960 --> 01:17:34,000 AND IN FACT, THERE WERE A FAIR 2268 01:17:34,000 --> 01:17:37,480 NUMBER OF ANTIBODIES AGAINST 2269 01:17:37,480 --> 01:17:38,120 INTERFERONS AS WELL AS AGAINST 2270 01:17:38,120 --> 01:17:38,960 OTHER CYTOKINES. 2271 01:17:38,960 --> 01:17:40,240 THEN THE QUESTION WAS, OKAY, IS 2272 01:17:40,240 --> 01:17:44,160 THAT CLINICALLY IMPORTANT? 2273 01:17:44,160 --> 01:17:45,760 WITHOUT GOING INTO HOW THEY MAKE 2274 01:17:45,760 --> 01:17:49,120 UP THESE SCORES, THERE IS THIS 2275 01:17:49,120 --> 01:17:50,360 OPPORTUNITY TO LOOK AT PATIENTS 2276 01:17:50,360 --> 01:17:52,200 WITH LUPUS AND LOOK AT THEIR 2277 01:17:52,200 --> 01:17:54,200 BLOOD AND SAY OKAY, WHAT GENES 2278 01:17:54,200 --> 01:17:56,120 ARE TURNED ON? 2279 01:17:56,120 --> 01:17:57,800 AND IT'S IN GENERAL THOUGHT THAT 2280 01:17:57,800 --> 01:18:03,640 LUPUS IS A DISEASE OF INTERFERON 2281 01:18:03,640 --> 01:18:05,000 ALPHA, OR TYPE I INTERFERON 2282 01:18:05,000 --> 01:18:06,360 ACTIVITY, OR AT LEAST THERE IS A 2283 01:18:06,360 --> 01:18:07,720 LOT OF INTERFERON ACTIVITY IN 2284 01:18:07,720 --> 01:18:10,800 IT, AND SO WE LOOKED FOR WHAT 2285 01:18:10,800 --> 01:18:12,520 WERE THE SIGNATURES FOR THAT. 2286 01:18:12,520 --> 01:18:16,600 AND SO IT TURNS OUT THAT IF 2287 01:18:16,600 --> 01:18:17,400 YOU'RE BLOCKING INTERFERON 2288 01:18:17,400 --> 01:18:19,040 GAMMA, THE LEVEL OF INTERFERON 2289 01:18:19,040 --> 01:18:20,200 ALPHA SIGNALING GOES UP. 2290 01:18:20,200 --> 01:18:21,640 AND WE'VE ACTUALLY SEEN THIS IN 2291 01:18:21,640 --> 01:18:23,000 THE GENETIC CONDITIONS AS WELL. 2292 01:18:23,000 --> 01:18:24,960 IF YOU BLOCK ONE, THE OTHER ONE 2293 01:18:24,960 --> 01:18:27,600 IS INCREASED. 2294 01:18:27,600 --> 01:18:29,600 SO IT TURNS OUT IF YOU WERE 2295 01:18:29,600 --> 01:18:31,040 BLOCKING INTERFERON GAMMA, YOUR 2296 01:18:31,040 --> 01:18:33,400 SCORE FOR INTERFERON ALPHA 2297 01:18:33,400 --> 01:18:36,720 ACTIVITY WAS HIGHER, SUGGESTING 2298 01:18:36,720 --> 01:18:38,840 POTENTIALLY WORSE LUPUS. 2299 01:18:38,840 --> 01:18:40,840 IN CONTRAST, THERE WERE OTHER 2300 01:18:40,840 --> 01:18:43,160 PEOPLE WHO HAD AUTO ANTIBODIES 2301 01:18:43,160 --> 01:18:46,640 AGAINST INFEAR ON INTERFERON ALPHA. 2302 01:18:46,640 --> 01:18:50,240 IF THEY HAD AUTO ANTIBODIES THAT 2303 01:18:50,240 --> 01:18:51,640 BLOCKED INTERFERON ALPHA, THAT 2304 01:18:51,640 --> 01:18:53,640 ACTUALLY MADE THEIR DEGREE OF 2305 01:18:53,640 --> 01:18:54,640 LUPUS SIGNIFICANTLY LESS IN 2306 01:18:54,640 --> 01:18:57,480 TERMS OF THE SCORING SYSTEM. 2307 01:18:57,480 --> 01:18:59,880 SO THIS SUGGESTS THAT 2308 01:18:59,880 --> 01:19:03,000 EPIGENETIC, AS IT WERE, 2309 01:19:03,000 --> 01:19:05,400 MODIFIERS OF LUPUS SCORES AND 2310 01:19:05,400 --> 01:19:07,080 LUPUS SEVERITY THAT OFTEN DON'T 2311 01:19:07,080 --> 01:19:10,000 GET TAKEN INTO ACCOUNT. 2312 01:19:10,000 --> 01:19:11,200 OKAY. 2313 01:19:11,200 --> 01:19:14,480 SO NOW WHAT ABOUT NOW THAT WE'VE 2314 01:19:14,480 --> 01:19:15,800 TALKED A LITTLE ABOUT RARE 2315 01:19:15,800 --> 01:19:17,440 DISEASE, ABOUT MORE COMMON 2316 01:19:17,440 --> 01:19:18,440 DISEASE, WHAT ABOUT REALLY 2317 01:19:18,440 --> 01:19:20,280 COMMON DISEASE? 2318 01:19:20,280 --> 01:19:21,760 WHAT ABOUT GOES ON IN PANDEMIC 2319 01:19:21,760 --> 01:19:22,000 DISEASE? 2320 01:19:22,000 --> 01:19:26,200 SO IN THIS REALLY ELEGANT STUDY 2321 01:19:26,200 --> 01:19:30,880 DONE, THEY WENT TO NORTHERN 2322 01:19:30,880 --> 01:19:32,320 ITALY TO OBTAIN SAMPLES FROM 2323 01:19:32,320 --> 01:19:34,840 PEOPLE WHO HAD SEVERE COVID-19 2324 01:19:34,840 --> 01:19:35,240 DISEASE. 2325 01:19:35,240 --> 01:19:40,520 AND THIS WAS LIKE ICU 2326 01:19:40,520 --> 01:19:40,840 SEVERE-SEVERE. 2327 01:19:40,840 --> 01:19:41,960 IN THE GENETIC PART OF THE 2328 01:19:41,960 --> 01:19:43,320 STUDY, WHAT YOU FOUND IS IF YOU 2329 01:19:43,320 --> 01:19:45,880 LOOK AT ONLY 13 GENES AROUND THE 2330 01:19:45,880 --> 01:19:47,200 RESPIRATORY SYSTEM AND HOW THE 2331 01:19:47,200 --> 01:19:48,240 VIRUSES RESPOND, THAT IS, CAN 2332 01:19:48,240 --> 01:19:49,560 YOU SENSE THE VIRUS, CAN YOU 2333 01:19:49,560 --> 01:19:53,320 RESPOND TO THE VIRUS BY MAKING 2334 01:19:53,320 --> 01:19:58,840 INTERFERONS, ONLY ABOUT 3 1/2% 2335 01:19:58,840 --> 01:19:59,960 OF PEOPLE HAD MUTATIONS IN GENES 2336 01:19:59,960 --> 01:20:00,520 AROUND THAT. 2337 01:20:00,520 --> 01:20:03,080 THAT IS, THEY HAD MONOGENIC 2338 01:20:03,080 --> 01:20:04,040 PROBLEMS THAT PREDISPOSE THEM TO 2339 01:20:04,040 --> 01:20:07,560 GETTING SEVERE COVID-19 DISEASE, 2340 01:20:07,560 --> 01:20:08,480 BECAUSE THEY COULD EITHER NOT 2341 01:20:08,480 --> 01:20:11,200 SENSE OR NOT RESPOND TO 2342 01:20:11,200 --> 01:20:12,080 INFECTION. 2343 01:20:12,080 --> 01:20:13,520 HERE YOU SEE SENSING AND HERE 2344 01:20:13,520 --> 01:20:22,160 YOU SEE THE INTERFERON RESPONSE. 2345 01:20:22,160 --> 01:20:23,840 AND THAT CORRESPONDED TO THIS 2346 01:20:23,840 --> 01:20:24,360 TYPE OF PROBLEM. 2347 01:20:24,360 --> 01:20:26,440 SO IF YOU LOOK AT THOSE PEOPLE 2348 01:20:26,440 --> 01:20:28,200 WHO HAD MUTATIONS IN KNOWS GENES 2349 01:20:28,200 --> 01:20:29,840 IN PEOPLE WHO WERE EITHER VIRAL 2350 01:20:29,840 --> 01:20:30,800 SENSING OR RESPONSE, AND YOU 2351 01:20:30,800 --> 01:20:32,080 LOOK AT THE LEVEL OF INTERFERON 2352 01:20:32,080 --> 01:20:33,400 ALPHA IN THEIR BLOOD, WHAT YOU 2353 01:20:33,400 --> 01:20:34,840 SEE IS THAT IF YOU CAN'T SENSE 2354 01:20:34,840 --> 01:20:37,680 THE VIRUS OR YOU CAN'T MAKE THE 2355 01:20:37,680 --> 01:20:38,840 INTERFERON, THEN, IN FACT, 2356 01:20:38,840 --> 01:20:43,000 YOU'VE GOT NO INTERFERON ALPHA, 2357 01:20:43,000 --> 01:20:44,800 TYPE I INTERFERON, DETECTABLE IN 2358 01:20:44,800 --> 01:20:45,240 YOUR BLOOD. 2359 01:20:45,240 --> 01:20:47,080 THIS IS WHAT THE NORMAL LEVEL 2360 01:20:47,080 --> 01:20:49,080 LOOKS LIKE IN PEOPLE WHO ARE 2361 01:20:49,080 --> 01:20:51,160 GETTING SICK WITH COVID-19. 2362 01:20:51,160 --> 01:20:52,520 SO THAT MAKES GOOD SENSE. 2363 01:20:52,520 --> 01:20:54,960 INTERFERON IS IMPORTANT IN 2364 01:20:54,960 --> 01:20:55,640 CONTROLLING VIRUSES. 2365 01:20:55,640 --> 01:20:56,880 THESE PEOPLE CAN'T DO THAT, 2366 01:20:56,880 --> 01:21:00,800 THEREFORE, THEY'RE GETTING SICK. 2367 01:21:00,800 --> 01:21:02,000 BUT IT TURNED OUT THERE WAS 2368 01:21:02,000 --> 01:21:04,440 ANOTHER SET OF PEOPLE WHO HAD 2369 01:21:04,440 --> 01:21:06,960 SEVERE DISEASE, WHO ALSO DIDN'T 2370 01:21:06,960 --> 01:21:09,240 HAVE DETECTABLE INTERFERON IN 2371 01:21:09,240 --> 01:21:15,400 THEIR PERIPHERAL BLOOD. 2372 01:21:15,400 --> 01:21:17,040 THIS TAKES US RIGHT BACK TO THE 2373 01:21:17,040 --> 01:21:18,840 BEGINNING BECAUSE THIS LOOKS 2374 01:21:18,840 --> 01:21:21,240 LIKE A GENETIC DISEASE, THIS ACT 2375 01:21:21,240 --> 01:21:22,520 LIKE A GENETIC DISEASE, BUT IT'S 2376 01:21:22,520 --> 01:21:26,040 COMING ON LATE IN LIFE. 2377 01:21:26,040 --> 01:21:28,240 AND THE IN VITRO CELLULAR 2378 01:21:28,240 --> 01:21:29,040 BEHAVIOR IS NORMAL. 2379 01:21:29,040 --> 01:21:30,400 SO WHAT'S GOING ON HERE? 2380 01:21:30,400 --> 01:21:31,480 WELL, YOU'VE ALREADY GUESSED IT. 2381 01:21:31,480 --> 01:21:33,840 THESE PEOPLE HAVE AUTO 2382 01:21:33,840 --> 01:21:35,200 ANTIBODIES, NOW NOT AGAINST 2383 01:21:35,200 --> 01:21:36,920 INTERFERON GAMMA, AGAINST 2384 01:21:36,920 --> 01:21:39,120 ANOTHER INTERFERON CALLED EITHER 2385 01:21:39,120 --> 01:21:41,440 ALPHA OROMAY GA. 2386 01:21:41,440 --> 01:21:44,320 OR OWE MAY TBA. 2387 01:21:44,320 --> 01:21:45,840 OMEGA. 2388 01:21:45,840 --> 01:21:47,200 WHAT THIS IS SHOWING IS A LOT OF 2389 01:21:47,200 --> 01:21:49,000 PEOPLE WHO ARE LIFE-THREATENING 2390 01:21:49,000 --> 01:21:50,320 COVID-19 DISEASE WHO DIDN'T HAVE 2391 01:21:50,320 --> 01:21:51,840 MUTATIONS HAD THESE AUTO 2392 01:21:51,840 --> 01:21:52,840 ANTIBODIES AGAINST INTERFERON 2393 01:21:52,840 --> 01:21:55,760 ALPHA OR INTERFERON OMEGA. 2394 01:21:55,760 --> 01:21:58,280 THE RATE OF THOSE ANTIBODIES WAS 2395 01:21:58,280 --> 01:22:00,200 MUCH HIGHER IN THOSE WITH 2396 01:22:00,200 --> 01:22:00,680 LIFE-THREATENING DISEASE 2397 01:22:00,680 --> 01:22:02,360 COMPARED TO THOSE WHO WERE 2398 01:22:02,360 --> 01:22:03,240 ASYMPTOMATIC OR HEALTHY 2399 01:22:03,240 --> 01:22:03,840 CONTROLS. 2400 01:22:03,840 --> 01:22:06,760 AND THOSE ANTIBODIES BLOCKED ALL 2401 01:22:06,760 --> 01:22:07,320 OF THE SIGNAL. 2402 01:22:07,320 --> 01:22:11,800 SO YES WE HAD PROBLEMS IN SOME 2403 01:22:11,800 --> 01:22:13,360 OF THE GENES IN A SMALL NUMBER, 2404 01:22:13,360 --> 01:22:16,920 BUT ALMOST THREE TIMES AS MANY 2405 01:22:16,920 --> 01:22:18,880 PATIENTS AS HAD GENETIC PROBLEMS 2406 01:22:18,880 --> 01:22:22,640 HAD ACQUIRED PROBLEMS THESE AUTO 2407 01:22:22,640 --> 01:22:22,960 ANTIBODIES. 2408 01:22:22,960 --> 01:22:28,440 NOW IT'S STILL A LITTLE UNCLEAR 2409 01:22:28,440 --> 01:22:30,240 WHAT IS CART AND WHAT IS HORSE. 2410 01:22:30,240 --> 01:22:32,000 IN STUDIES DONE HERE, WE KNOW 2411 01:22:32,000 --> 01:22:36,280 THERE IS A VERY DYNAMIC RATE TO 2412 01:22:36,280 --> 01:22:36,640 THESE. 2413 01:22:36,640 --> 01:22:37,640 THEY GO UP A LITTLE BIT EARLY IN 2414 01:22:37,640 --> 01:22:39,240 THE DISEASE, AND THEN OVER THE 2415 01:22:39,240 --> 01:22:41,640 COURSE OF TIME, THESE ANTIBODIES 2416 01:22:41,640 --> 01:22:43,160 FALL BACK DOWN TO THE NORMAL 2417 01:22:43,160 --> 01:22:44,080 LEVEL. 2418 01:22:44,080 --> 01:22:46,120 SO THEY ARE DYNAMIC AND SO 2419 01:22:46,120 --> 01:22:47,760 THEY'RE GOING TO BE CHANGING 2420 01:22:47,760 --> 01:22:53,240 OVER THE COURSE OF DISEASE. 2421 01:22:53,240 --> 01:22:54,320 LASTLY, ONCE YOU LIGHT THE FUSE, 2422 01:22:54,320 --> 01:23:02,640 IT'S HARD TO KNOW WHAT GOES OFF. 2423 01:23:02,640 --> 01:23:04,480 THIS IS DR. CRISWELL'S ALMA 2424 01:23:04,480 --> 01:23:04,680 MATER. 2425 01:23:04,680 --> 01:23:06,000 IF YOU LOOK AT THE CHANGE IN 2426 01:23:06,000 --> 01:23:07,800 AUTO ANTIBODIES IN PEOPLE WHO 2427 01:23:07,800 --> 01:23:10,160 HAVE BEEN INFECTED OVER THE 2428 01:23:10,160 --> 01:23:14,520 COURSE OF THEIR HOSPITALIZATION, 2429 01:23:14,520 --> 01:23:15,840 WHAT YOU SEE IS BEING INFECTED 2430 01:23:15,840 --> 01:23:17,200 WITH COVID-19 CAN TRIGGER THE 2431 01:23:17,200 --> 01:23:19,000 DEVELOPMENT OF AUTO ANTIBODIES 2432 01:23:19,000 --> 01:23:23,000 AGAINST A VARIETY OF MOLECULES, 2433 01:23:23,000 --> 01:23:23,640 INCLUDING INTERLEUKINS, 2434 01:23:23,640 --> 01:23:25,440 INTERFERONS, AND OTHER 2435 01:23:25,440 --> 01:23:26,600 CYTOKINES. 2436 01:23:26,600 --> 01:23:29,280 SO THIS IS BOTH SOMETHING THAT 2437 01:23:29,280 --> 01:23:31,440 IS AFFECTED BY HAVING AUTO 2438 01:23:31,440 --> 01:23:35,360 ANTIBODIES, AND MAY BE 2439 01:23:35,360 --> 01:23:39,720 GENERATING AUTO ANTIBODIES. 2440 01:23:39,720 --> 01:23:40,280 OKAY. 2441 01:23:40,280 --> 01:23:42,880 SO I'M DONE WITH THE 2442 01:23:42,880 --> 01:23:43,640 EXPOSITIONAL PART AND I WILL 2443 01:23:43,640 --> 01:23:45,040 JUST SAY HERE I HAVE MERCIFULLY 2444 01:23:45,040 --> 01:23:46,360 SPARED YOU FROM HEARING ABOUT 2445 01:23:46,360 --> 01:23:47,840 ANYTHING OTHER THAN JUST 2446 01:23:47,840 --> 01:23:49,560 INTERFERON GAMMA AND THE TYPE 2447 01:23:49,560 --> 01:23:50,000 1 INTERFERONS. 2448 01:23:50,000 --> 01:23:51,400 BUT THAT'S NOT BECAUSE THERE'S 2449 01:23:51,400 --> 01:23:52,440 NOTHING ELSE TO SAY. 2450 01:23:52,440 --> 01:23:54,400 AND THERE ARE AUTO ANTIBODIES TO 2451 01:23:54,400 --> 01:23:57,080 A VARIETY OF OTHER CYTOKINES AND 2452 01:23:57,080 --> 01:24:03,520 THOSE ARE MODIFYING AND CAUSING 2453 01:24:03,520 --> 01:24:04,400 DISEASE HAVE NOT YET BEEN SORTED 2454 01:24:04,400 --> 01:24:05,040 OUT. 2455 01:24:05,040 --> 01:24:06,840 SO THESE ANTICYTOKINE AUTO 2456 01:24:06,840 --> 01:24:08,520 ANTIBODIES ARE ACQUIRED INNATE 2457 01:24:08,520 --> 01:24:10,280 AND ADAPTIVE IMMUNE DEFECTS THAT 2458 01:24:10,280 --> 01:24:12,920 ARE DYNAMIC, THEY CAN HAVE 2459 01:24:12,920 --> 01:24:14,240 ON-TARGET AND OFF-TARGET 2460 01:24:14,240 --> 01:24:16,240 EFFECTS, AND WE CAN TREAT THEM, 2461 01:24:16,240 --> 01:24:19,880 AND I AM SURE THAT THEY CAUSE 2462 01:24:19,880 --> 01:24:23,960 MORE DISEASE THAN WE THINK. 2463 01:24:23,960 --> 01:24:25,400 SO SO WE START TALKING ABOUT 2464 01:24:25,400 --> 01:24:26,760 GENETICS AND WE WOUND UP TALKING 2465 01:24:26,760 --> 01:24:27,360 ABOUT EPIGENETICS. 2466 01:24:27,360 --> 01:24:31,760 AND SO I JUST WANT TO REMINE REMIND YOU 2467 01:24:31,760 --> 01:24:32,680 THERE'S GENOTYPE AND THERE'S 2468 01:24:32,680 --> 01:24:34,440 PHENOTYPE. 2469 01:24:34,440 --> 01:24:38,040 GENOTYPE MOSTLY SAYS THE SAME, 2470 01:24:38,040 --> 01:24:40,640 BUT PHENOTYPE CHANGES WITH TIME, 2471 01:24:40,640 --> 01:24:41,520 EXPOSURE, ENVIRONMENT, AND I 2472 01:24:41,520 --> 01:24:44,360 DARE SAY WITH SATISFACTION. 2473 01:24:44,360 --> 01:24:46,680 SO I JUST WANT TO STOP AND 2474 01:24:46,680 --> 01:24:48,160 ACKNOWLEDGE MY EXTRAORDINARY 2475 01:24:48,160 --> 01:24:49,840 COLLEAGUES HERE. 2476 01:24:49,840 --> 01:24:53,880 LINDSEY ROSEN, CHRISTA, SARAH, 2477 01:24:53,880 --> 01:24:55,160 AND LEE HAVE REALLY BEEN THE 2478 01:24:55,160 --> 01:24:57,520 ONES DRIVING OUR AUTO ANTIBODY 2479 01:24:57,520 --> 01:24:58,640 WORK AS WELL AS MANY 2480 01:24:58,640 --> 01:24:59,720 COLLABORATORS THAT HAVE BEEN 2481 01:24:59,720 --> 01:25:01,160 INVOLVED ESPECIALLY FOR THE 2482 01:25:01,160 --> 01:25:04,160 COVID WORK WITH GIGI, HELEN AND 2483 01:25:04,160 --> 01:25:05,880 ALA INSURING A. 2484 01:25:05,880 --> 01:25:07,240 OUR TERRIFIC COLLABORATORS IN 2485 01:25:07,240 --> 01:25:11,640 THE DENTAL INSTITUTE IN ATHENS, 2486 01:25:11,640 --> 01:25:14,920 IN THAILAND, AND IN THE HUMAN 2487 01:25:14,920 --> 01:25:16,520 GENOME PROJECT, AND THEN OUR 2488 01:25:16,520 --> 01:25:17,840 COLLABORATORS IN NIAMS, 2489 01:25:17,840 --> 01:25:18,760 DR. CRISWELL, THIS IS NOT FOR 2490 01:25:18,760 --> 01:25:20,040 YOUR BENEFIT, BUT I WILL JUST 2491 01:25:20,040 --> 01:25:22,440 SAY THEY HAVE BEEN EXTRAORDINARY 2492 01:25:22,440 --> 01:25:25,200 COLLABORATOR, DR. GUPTA, AND 2493 01:25:25,200 --> 01:25:26,000 OTHERS AS WELL. 2494 01:25:26,000 --> 01:25:29,800 AND SO I WILL STOP THERE AND I 2495 01:25:29,800 --> 01:25:30,840 LOOK FORWARD TO A CHANCE TO 2496 01:25:30,840 --> 01:25:32,480 INTERACT OVER QUESTIONS. 2497 01:25:32,480 --> 01:25:33,760 >> WELL, THANK YOU SO MUCH, 2498 01:25:33,760 --> 01:25:36,840 DR. HO LAND, HOLLAND, FOR THAT 2499 01:25:36,840 --> 01:25:37,240 SPECTACULAR TALK. 2500 01:25:37,240 --> 01:25:40,840 SO AT THIS POINT, WE WILL GATHER 2501 01:25:40,840 --> 01:25:44,840 TOGETHER OUR VARIOUS PRESENTERS. 2502 01:25:44,840 --> 01:25:49,920 JENNIFER AND DR. CRISWELL AND 2503 01:25:49,920 --> 01:25:51,720 DR. HOLLAND, AND DR. ARIAS IS 2504 01:25:51,720 --> 01:25:54,000 HERE ON THE SCREEN TOO. 2505 01:25:54,000 --> 01:25:57,000 AND WE'LL JUST ENTERTAIN 2506 01:25:57,000 --> 01:25:57,960 QUESTIONS THAT WE HAVE AND 2507 01:25:57,960 --> 01:26:01,480 ACTUALLY WE HAVE GOTTEN A BUMPER 2508 01:26:01,480 --> 01:26:02,840 CROP OF QUESTIONS. 2509 01:26:02,840 --> 01:26:05,680 I DON'T EVEN KNOW IF WE'LL BE 2510 01:26:05,680 --> 01:26:06,960 ABLE TO GET THROUGH ALL OF THEM, 2511 01:26:06,960 --> 01:26:08,920 BUT CERTAINLY FOR THE ONES THAT 2512 01:26:08,920 --> 01:26:11,480 WE DON'T GET TO, WE CAN ALWAYS 2513 01:26:11,480 --> 01:26:14,000 ADDRESS THEM TO THE SPEAKERS 2514 01:26:14,000 --> 01:26:16,000 LATER ON AND GET BACK WITH YOU 2515 01:26:16,000 --> 01:26:17,960 WITH THE ANSWERS. 2516 01:26:17,960 --> 01:26:19,800 SO ONE QUESTION THAT COMES UP 2517 01:26:19,800 --> 01:26:23,480 THAT REALLY TIES TOGETHER THE 2518 01:26:23,480 --> 01:26:26,040 TWO TALKS HAS TO DO WITH THE 2519 01:26:26,040 --> 01:26:27,960 WHOLE ISSUE OF TYPE 2520 01:26:27,960 --> 01:26:29,480 1 INTERFERONS, AND THE FACT THAT 2521 01:26:29,480 --> 01:26:31,880 TYPE 1 INTERFERONS PLAY AN 2522 01:26:31,880 --> 01:26:33,520 IMPORTANT ROLE IN AUTOIMMUNE 2523 01:26:33,520 --> 01:26:36,200 DISEASES LIKE LUPUS, BUT ARE 2524 01:26:36,200 --> 01:26:37,680 ALSO IMPORTANT IN TERMS OF 2525 01:26:37,680 --> 01:26:39,320 RESISTANCE TO CERTAIN BACTERIAL 2526 01:26:39,320 --> 01:26:40,080 INFECTIONS. 2527 01:26:40,080 --> 01:26:45,560 AND SO THE QUESTIONER WANT TO 2528 01:26:45,560 --> 01:26:46,880 KNOW WHETHER IN PATIENTS WITH 2529 01:26:46,880 --> 01:26:48,480 LUPUS OR PERHAPS WITH OTHER 2530 01:26:48,480 --> 01:26:49,800 AUTOIMMUNE DISEASES, ARE THEY 2531 01:26:49,800 --> 01:26:51,480 MORE RESISTANT TO CERTAIN VIRAL 2532 01:26:51,480 --> 01:26:52,520 INFECTIONS? 2533 01:26:52,520 --> 01:26:54,640 AND THIS COULD REALLY BE 2534 01:26:54,640 --> 01:26:56,840 ADDRESSED BOTH TO DR. CRISWELL 2535 01:26:56,840 --> 01:27:02,760 AND TO DR. HOLLAND. 2536 01:27:02,760 --> 01:27:07,160 >> I'LL START AND STEVE MAY WAN 2537 01:27:07,160 --> 01:27:07,840 TO ADD. 2538 01:27:07,840 --> 01:27:11,360 THE RELATIONSHIP IS FASCINATING, 2539 01:27:11,360 --> 01:27:17,800 AND YOU KNOW, CHANGES OVER TIME, 2540 01:27:17,800 --> 01:27:18,800 INFECTIOUS THREATS IN THE 2541 01:27:18,800 --> 01:27:20,200 ENVIRONMENT HAVE PROBABLY 2542 01:27:20,200 --> 01:27:21,720 INFLUENCED OUR GENETICS IN SUCH 2543 01:27:21,720 --> 01:27:25,120 A WAY THAT IT'S RESULTED IN 2544 01:27:25,120 --> 01:27:27,280 PREDISPOSITION TO AUTOIMMUNE 2545 01:27:27,280 --> 01:27:29,800 DISEASES, SO REALLY COMPLICATED 2546 01:27:29,800 --> 01:27:31,160 RELATIONSHIPS BETWEEN AUTOIMMUNE 2547 01:27:31,160 --> 01:27:32,000 DISEASES AND INFECTION. 2548 01:27:32,000 --> 01:27:34,000 IN TERMS OF LUPUS AND VIRUSES, 2549 01:27:34,000 --> 01:27:39,000 THE MOST NOTABLE ASSOCIATION IS 2550 01:27:39,000 --> 01:27:39,640 SIGNIFICANT EVIDENCE THAT 2551 01:27:39,640 --> 01:27:42,520 CERTAIN VIRUS INFECTIONS CAN 2552 01:27:42,520 --> 01:27:46,320 TRIGGER THE ONSET OF LUPUS. 2553 01:27:46,320 --> 01:27:47,760 THE STRONGEST DATA IS FOR 2554 01:27:47,760 --> 01:27:50,640 EPSTEIN-BARR VIRUS, THE VIRUS 2555 01:27:50,640 --> 01:27:51,240 THAT CAUSES MONONUCLEOSIS. 2556 01:27:51,240 --> 01:27:52,360 THERE ARE ALSO CASE REPORTS OF 2557 01:27:52,360 --> 01:27:54,600 OTHER VIRUSES SUCH AS THE 2558 01:27:54,600 --> 01:27:57,520 VARICELLA VIRUS THAT CAUSES 2559 01:27:57,520 --> 01:27:59,520 CHICKEN POX AND SHINGLES, FOR 2560 01:27:59,520 --> 01:28:01,240 EXAMPLE, TRIGGERING THE ONSET OF 2561 01:28:01,240 --> 01:28:01,480 LUPUS. 2562 01:28:01,480 --> 01:28:02,520 JENNIFER DIDN'T MENTION BUT A 2563 01:28:02,520 --> 01:28:06,120 YEAR OR SO BEFORE SHE DEVELOPED 2564 01:28:06,120 --> 01:28:07,760 LUPUS, SHE HAD CHICKEN POX, AND 2565 01:28:07,760 --> 01:28:08,680 ONE MIGHT WONDER WHETHER THAT 2566 01:28:08,680 --> 01:28:10,240 MIGHT HAVE CONTRIBUTED TO 2567 01:28:10,240 --> 01:28:12,320 TRIGGERING HER DISEASE. 2568 01:28:12,320 --> 01:28:16,200 SO I'M NOT AWARE OF SUBSTANTIAL 2569 01:28:16,200 --> 01:28:17,600 EVIDENCE THAT'S SUGGESTIVE THAT 2570 01:28:17,600 --> 01:28:18,720 ONCE SOMEONE DEVELOPED LUPUS 2571 01:28:18,720 --> 01:28:20,640 THAT THEY'RE PROTECTED FROM 2572 01:28:20,640 --> 01:28:21,240 VIRUS INFECTIONS, BUT STEVE MAY 2573 01:28:21,240 --> 01:28:23,160 HAVE ANOTHER PERSPECTIVE ON THAT 2574 01:28:23,160 --> 01:28:23,440 QUESTION. 2575 01:28:23,440 --> 01:28:25,040 >> OKAY, WELL, LET'S SEE WHAT 2576 01:28:25,040 --> 01:28:26,000 STEVE HAS TO SAY. 2577 01:28:26,000 --> 01:28:28,520 >> I WOULD NEVER DISAGREE WITH 2578 01:28:28,520 --> 01:28:30,440 LINDSEY, AND I DON'T HERE. 2579 01:28:30,440 --> 01:28:33,600 I THINK, YOU KNOW, THE 2580 01:28:33,600 --> 01:28:36,200 LITERATURE ABOUT INFECTION 2581 01:28:36,200 --> 01:28:37,440 SUSCEPTIBILITY IN A LOT OF THE 2582 01:28:37,440 --> 01:28:38,840 AUTOIMMUNE DISEASES IS HEAVILY 2583 01:28:38,840 --> 01:28:42,000 AFFECTED BY TREATMENT. 2584 01:28:42,000 --> 01:28:44,520 SO STEROIDS CLEARLY INCREASE THE 2585 01:28:44,520 --> 01:28:45,480 RISK OF INFECTION. 2586 01:28:45,480 --> 01:28:46,480 MANY OF THESE OTHER DRUGS 2587 01:28:46,480 --> 01:28:47,880 INCREASE THE RISK OF INFECTION. 2588 01:28:47,880 --> 01:28:49,600 ONE OF THE FASCINATING THINGS IS 2589 01:28:49,600 --> 01:28:52,320 THAT IN ALMOST ALL OF THE PRIME 2590 01:28:52,320 --> 01:28:55,640 RYE 2591 01:28:55,640 --> 01:28:56,560 PRIMARY IMMUNE DEFICIENCIES, 2592 01:28:56,560 --> 01:28:59,240 WHERE YOU'VE GOT A LOT OF 2593 01:28:59,240 --> 01:29:00,240 INFECTION SUSCEPTIBILITY, IT'S 2594 01:29:00,240 --> 01:29:01,160 COUPLED TO THE INCREASE IN THE 2595 01:29:01,160 --> 01:29:04,240 RATE OF AUTO AUTOIMMUNITY. 2596 01:29:04,240 --> 01:29:05,360 EXACTLY WHY THAT IS, I DON'T 2597 01:29:05,360 --> 01:29:07,760 KNOW, BUT I WOULD CERTAINLY 2598 01:29:07,760 --> 01:29:09,640 DEFER -- I THINK THAT LUPUS, PER 2599 01:29:09,640 --> 01:29:16,720 SE, IS NOT AN INFECTION 2600 01:29:16,720 --> 01:29:17,200 AGGREGATING DISEASE. 2601 01:29:17,200 --> 01:29:18,560 IT MAY BE TRIGGERED BY AN 2602 01:29:18,560 --> 01:29:20,160 INFECTION BUT THEY DON'T GET 2603 01:29:20,160 --> 01:29:21,440 MORE BACTERIAL INFECTIONS IN THE 2604 01:29:21,440 --> 01:29:22,200 ABSENCE OF THERAPY THAT I'M 2605 01:29:22,200 --> 01:29:23,760 FAMILIAR WITH. 2606 01:29:23,760 --> 01:29:25,240 >> AND JUST FOLLOWING UP A 2607 01:29:25,240 --> 01:29:29,080 LITTLE BIT ON WHAT LINDSEY HAD 2608 01:29:29,080 --> 01:29:37,640 RAISED THE QUESTION OF WHETHER 2609 01:29:37,640 --> 01:29:41,880 PERHAPS THE SELECTION FOR 2610 01:29:41,880 --> 01:29:42,600 RESPONSIVENESS TO CERTAIN 2611 01:29:42,600 --> 01:29:47,240 PATHOGENS MIGHT INCREASE THE 2612 01:29:47,240 --> 01:29:49,160 FREQUENCY OF VARIANTS THAT 2613 01:29:49,160 --> 01:29:50,520 INCREASE IMMUNE RESPONSIVENESS, 2614 01:29:50,520 --> 01:29:54,480 INTERFERON PRODUCTION OR 2615 01:29:54,480 --> 01:29:55,080 WHATEVER, IS THERE ANY DIRECT 2616 01:29:55,080 --> 01:29:56,080 EVIDENCE OF THAT, LINDSEY, THAT 2617 01:29:56,080 --> 01:30:01,120 YOU KNOW OF IN TERMS OF STUDIES 2618 01:30:01,120 --> 01:30:05,080 OF GENOME STRUCTURE, LOOKING FOR 2619 01:30:05,080 --> 01:30:06,600 LARGE HAPLOTYPES, LET'S SAY THAT 2620 01:30:06,600 --> 01:30:10,280 WOULD BE ASSOCIATED WITH 2621 01:30:10,280 --> 01:30:14,280 PARTICULAR VARIANTS OF 2622 01:30:14,280 --> 01:30:15,600 INTERFERON-RELATED GENES IN THE 2623 01:30:15,600 --> 01:30:16,160 GENERAL POPULATION? 2624 01:30:16,160 --> 01:30:18,000 >> I'M AFRAID I'M NOT AWARE OF 2625 01:30:18,000 --> 01:30:19,640 DIRECT EVIDENCE, BUT THERE ARE A 2626 01:30:19,640 --> 01:30:21,600 NUMBER OF VERY ATTRACTIVE 2627 01:30:21,600 --> 01:30:22,960 THEORIES THAT WOULD CONNECT 2628 01:30:22,960 --> 01:30:23,720 THOSE TWO THINGS. 2629 01:30:23,720 --> 01:30:28,240 FOR EXAMPLE, THERE'S A GENETIC 2630 01:30:28,240 --> 01:30:31,720 RISK VARIANT, A FUNCTIONAL 2631 01:30:31,720 --> 01:30:33,960 VARIANT, PNTP22 ASSOCIATED WITH 2632 01:30:33,960 --> 01:30:35,480 MANY AUTOIMMUNE DISEASES AND HAS 2633 01:30:35,480 --> 01:30:37,240 VERY STRIKING VARIATION IN 2634 01:30:37,240 --> 01:30:39,760 ALLELE FREQUENCY WITHIN EUROPE, 2635 01:30:39,760 --> 01:30:46,120 FOR EXAMPLE, WITH VERY HIGH 2636 01:30:46,120 --> 01:30:48,400 FREQUENCY IN THE NORTH, LOW 2637 01:30:48,400 --> 01:30:50,560 FREQUENCY IN THE SOUTH, FOR 2638 01:30:50,560 --> 01:30:52,520 EXAMPLE, . 2639 01:30:52,520 --> 01:30:54,640 AN ATTRACTIVE HYPOTHESIS IS THAT 2640 01:30:54,640 --> 01:30:55,720 PATTERN, DIFFERENCE IN ALLELE 2641 01:30:55,720 --> 01:30:59,120 FREQUENCY, REFLECTS AN 2642 01:30:59,120 --> 01:30:59,720 INFECTIOUS DISEASE -- PERHAPS 2643 01:30:59,720 --> 01:31:02,880 THE PLAGUE THAT WENT THROUGH 2644 01:31:02,880 --> 01:31:04,480 EUROPE AND RESULTED IN SELECTION 2645 01:31:04,480 --> 01:31:05,840 FOR CERTAIN VARIANTS THAT 2646 01:31:05,840 --> 01:31:06,560 PROTECTED AGAINST DISEASE THAT 2647 01:31:06,560 --> 01:31:10,640 HAVE AS A CONSEQUENCE NOW 2648 01:31:10,640 --> 01:31:14,640 AFRICAN AMERICAN AN 2649 01:31:14,640 --> 01:31:15,560 INCREASED RISK OF AUTOIMMUNE 2650 01:31:15,560 --> 01:31:15,920 DISEASES. 2651 01:31:15,920 --> 01:31:18,240 I'M NOT AWARE OF THE SORT OF 2652 01:31:18,240 --> 01:31:19,600 EVIDENCE THAT YOU ALLUDED TO, 2653 01:31:19,600 --> 01:31:19,840 DAN. 2654 01:31:19,840 --> 01:31:21,760 ONCE AGAIN, PERHAPS STEVE IS 2655 01:31:21,760 --> 01:31:25,280 AWARE OF SOME EVIDENCE ON THAT 2656 01:31:25,280 --> 01:31:25,480 FRONT. 2657 01:31:25,480 --> 01:31:26,760 >> STEVE IS SHAKING HIS HEAD 2658 01:31:26,760 --> 01:31:31,240 KNOW, BUT THIS IS JUST, I GUESS, 2659 01:31:31,240 --> 01:31:33,400 AN OPPORTUNITY FOR MORE RESEARCH 2660 01:31:33,400 --> 01:31:37,120 FOLLOWING UP ON THAT PTPN 2661 01:31:37,120 --> 01:31:39,600 22 VARIANT, PRANCE PERHAPS THERE'S 2662 01:31:39,600 --> 01:31:40,600 SOMETHING MORE THERE THAT CAN BE 2663 01:31:40,600 --> 01:31:42,080 FOUND, BUT IT'S A VERY 2664 01:31:42,080 --> 01:31:42,680 FASCINATING IDEA THAT PERHAPS 2665 01:31:42,680 --> 01:31:46,280 THAT HIGH FREQUENCY IN NORTHERN 2666 01:31:46,280 --> 01:31:47,240 EUROPEAN POPULATIONS IS THERE 2667 01:31:47,240 --> 01:31:50,880 FOR A REASON OF SOME SORT. 2668 01:31:50,880 --> 01:31:52,600 ALL RIGHT. 2669 01:31:52,600 --> 01:31:56,680 WELL, NOW THAT I'VE PICKED ON 2670 01:31:56,680 --> 01:31:58,200 DOCTORS HOLLAND AND CRISWELL, 2671 01:31:58,200 --> 01:31:59,600 NOW IT'S TIME TO GO BACK TO 2672 01:31:59,600 --> 01:31:59,920 JENNIFER. 2673 01:31:59,920 --> 01:32:01,320 SHE THOUGHT SHE WAS OFF THE HOOK 2674 01:32:01,320 --> 01:32:02,840 BUT THAT HOOK IS A PRETTY BIG 2675 01:32:02,840 --> 01:32:05,640 ONE HERE. 2676 01:32:05,640 --> 01:32:08,240 AND SO HERE IS A QUESTION FROM 2677 01:32:08,240 --> 01:32:08,640 CATHY. 2678 01:32:08,640 --> 01:32:12,960 THE QUESTION IS, HOW MUCH DOES 2679 01:32:12,960 --> 01:32:14,880 DIET CONTRIBUTE TO FLARE-UPS IN 2680 01:32:14,880 --> 01:32:18,200 THE BODY, AND WHAT ARE THE FOODS 2681 01:32:18,200 --> 01:32:19,680 YOU ENJOY TO ALLEVIATE SWELLING 2682 01:32:19,680 --> 01:32:20,240 IN THE BODY? 2683 01:32:20,240 --> 01:32:22,240 I GUESS THAT I COULD ADD ANOTHER 2684 01:32:22,240 --> 01:32:22,840 QUESTION TO IT. 2685 01:32:22,840 --> 01:32:25,000 I WAS TRYING TO THINK UP 2686 01:32:25,000 --> 01:32:28,880 QUESTIONS JUST IN CASE NOBODY 2687 01:32:28,880 --> 01:32:29,960 ASKED ANY QUESTIONS, SO THERE'S 2688 01:32:29,960 --> 01:32:33,000 THE VITAMIN D DEFICIENCY ISSUE 2689 01:32:33,000 --> 01:32:35,040 ASSOCIATED WITH AUTOIMMUNITY, 2690 01:32:35,040 --> 01:32:38,840 AND WOULD A DIET RICH IN DAIRY 2691 01:32:38,840 --> 01:32:40,000 PRODUCT LIKE ICE CREAM, WOULD 2692 01:32:40,000 --> 01:32:42,120 THAT, PERHAPS, HELP WITH AN 2693 01:32:42,120 --> 01:32:44,960 AUTOIMMUNE DISEASE? 2694 01:32:44,960 --> 01:32:46,840 >> WELL, AS SOMEBODY WHO ENJOYS 2695 01:32:46,840 --> 01:32:51,680 ICE CREAM BUT IS ALSO LACTOSE 2696 01:32:51,680 --> 01:32:53,280 INTOLERANT, IT'S A FASCINATING 2697 01:32:53,280 --> 01:32:57,000 QUESTION AND I WILL SAY THAT 2698 01:32:57,000 --> 01:32:59,320 FOR -- I'VE HAD G.I. CHALLENGES 2699 01:32:59,320 --> 01:33:02,040 AS FAR BACK AS MY TEENAGE YEARS. 2700 01:33:02,040 --> 01:33:03,080 THEY PERSIST. 2701 01:33:03,080 --> 01:33:06,000 AND FOR YEARS, MY DOCTORS 2702 01:33:06,000 --> 01:33:07,320 INCLUDING MY RHEUMATOLOGISTS HAD 2703 01:33:07,320 --> 01:33:09,320 SUGGESTED A GLUTEN-FREE DIET 2704 01:33:09,320 --> 01:33:11,560 POTENTIALLY. 2705 01:33:11,560 --> 01:33:16,240 I DID GO GLUTEN-FREE, GOSH, 2706 01:33:16,240 --> 01:33:18,200 PROBABLY WELL OVER A DECADE AGO. 2707 01:33:18,200 --> 01:33:19,480 THAT DID HELP. 2708 01:33:19,480 --> 01:33:24,320 I FOUND THAT GOING LOW FODMOP, 2709 01:33:24,320 --> 01:33:27,400 SUGARS THAT CAN BE HARD TO TIE 2710 01:33:27,400 --> 01:33:29,120 TIE-DYE 2711 01:33:29,120 --> 01:33:32,640 DIGEST, THEY CAN FERMENT IN THE 2712 01:33:32,640 --> 01:33:34,960 GUT, THAT IN ADDITION WITH BEING 2713 01:33:34,960 --> 01:33:38,160 BLUE 10-FREE 2714 01:33:38,160 --> 01:33:39,520 GLUTEN-FREE HAS HELPED. 2715 01:33:39,520 --> 01:33:40,840 I'VE NOT NOTICED A CORRELATION 2716 01:33:40,840 --> 01:33:41,920 WITH MY ARTHRITIS, THOUGH, AND I 2717 01:33:41,920 --> 01:33:44,160 WOULD LEAVE TO DRS. CRISWELL AND 2718 01:33:44,160 --> 01:33:45,440 HOLLAND TO MAYBE COMMENT ON 2719 01:33:45,440 --> 01:33:45,640 THAT. 2720 01:33:45,640 --> 01:33:47,160 >> BEFORE THEY DO, SO WHAT ARE 2721 01:33:47,160 --> 01:33:51,000 YOU LEFT TO EAT IF YOU'RE 2722 01:33:51,000 --> 01:33:52,520 AVOIDING ALL OF THESE THINGS? 2723 01:33:52,520 --> 01:33:54,240 >> THERE'S PLENTY LEFT TO EAT, 2724 01:33:54,240 --> 01:33:56,080 AND FORTUNATELY WE'RE IN AN AGE 2725 01:33:56,080 --> 01:33:59,320 NOW WITH THESE HAN TEE HANDY APPS ON OUR 2726 01:33:59,320 --> 01:34:00,560 IPHONES WHEN FACEED WITH A PLATE 2727 01:34:00,560 --> 01:34:01,640 OF SOMETHING DELICIOUS, YOU CAN 2728 01:34:01,640 --> 01:34:05,160 TYPE IN THAT FOOD AND SEE HOW 2729 01:34:05,160 --> 01:34:06,360 COMFORTABLE YOUR NEXT 24 HOURS 2730 01:34:06,360 --> 01:34:09,040 WILL BE SHOULD YOU PARTAKE. 2731 01:34:09,040 --> 01:34:11,080 >> HOPEFULLY THE APP ON YOUR 2732 01:34:11,080 --> 01:34:12,760 PHONE ALLOWS YOU TO EAT 2733 01:34:12,760 --> 01:34:13,240 SOMETHING, THOUGHMENT 2734 01:34:13,240 --> 01:34:14,560 >> YES. 2735 01:34:14,560 --> 01:34:16,800 NO, I'M CERTAINLY -- I DON'T GO 2736 01:34:16,800 --> 01:34:17,840 WITHOUT, I'LL SAY THAT. 2737 01:34:17,840 --> 01:34:18,640 >> ALL RIGHT. 2738 01:34:18,640 --> 01:34:20,320 WELL, LET'S SEE IF DR. CRISWELL 2739 01:34:20,320 --> 01:34:22,000 OR DR. HOLLAND HAVE ANYTHING TO 2740 01:34:22,000 --> 01:34:27,560 ADD TO THOSE COMMENTS. 2741 01:34:27,560 --> 01:34:31,280 >> STUDIES OF DIET AND YOU 2742 01:34:31,280 --> 01:34:32,000 AUTOIMMUNE DISEASE ARE 2743 01:34:32,000 --> 01:34:33,200 CHALLENGING FOR A NUMBER OF 2744 01:34:33,200 --> 01:34:37,120 REASONS, STUDY DESIGN ISSUES, ET 2745 01:34:37,120 --> 01:34:37,640 CETERA. 2746 01:34:37,640 --> 01:34:39,440 I'VE BEEN INTERESTED TO SEE SOME 2747 01:34:39,440 --> 01:34:41,160 IMPRESSIVE DATA IN TERMS OF THE 2748 01:34:41,160 --> 01:34:44,800 QUALITY OF THE STUDY COMING OUT 2749 01:34:44,800 --> 01:34:46,000 OF THE OSTEOARTHRITIS 2750 01:34:46,000 --> 01:34:48,800 LITERATURE, IMPLICATING CERTAIN 2751 01:34:48,800 --> 01:34:50,360 DIETS THAT THEY CHARACTERIZE 2752 01:34:50,360 --> 01:34:54,840 DIETS IN TERMS OF WESTERN DIET 2753 01:34:54,840 --> 01:34:56,320 VERSUS PRUDENT DIET BEING MORE 2754 01:34:56,320 --> 01:34:58,000 LIKE THE MEDITERRANEAN DIET, AND 2755 01:34:58,000 --> 01:34:59,720 OVER YEARS OF OBSERVATION WITH 2756 01:34:59,720 --> 01:35:03,200 IMAGING STUDY, ET CETERA, 2757 01:35:03,200 --> 01:35:04,720 OSTEOARTHRITIS PROGRESSED MORE 2758 01:35:04,720 --> 01:35:06,160 RAPIDLY AMONG INDIVIDUALS WHO 2759 01:35:06,160 --> 01:35:10,440 WERE CONSUMING A HIGH WESTERN 2760 01:35:10,440 --> 01:35:12,440 DIET COMPARED TO THOSE WITH THE 2761 01:35:12,440 --> 01:35:13,840 PRUDENT DIE E I WAS IMPRESSED 2762 01:35:13,840 --> 01:35:16,000 THAT WAS NOT FULLY EXPLAINED, 2763 01:35:16,000 --> 01:35:17,040 ONLY PARTIALLY EXPLAINED BY 2764 01:35:17,040 --> 01:35:18,160 WEIGHT AND BMI. 2765 01:35:18,160 --> 01:35:19,680 SO I THINK THERE IS STILL A LOT 2766 01:35:19,680 --> 01:35:23,120 TO LEARN IN TERMS OF DIET AND 2767 01:35:23,120 --> 01:35:24,440 ARTHRITIS AND OTHER 2768 01:35:24,440 --> 01:35:27,440 MANIFESTATIONS OF LUPUS. 2769 01:35:27,440 --> 01:35:28,360 >> ALL RIGHT. 2770 01:35:28,360 --> 01:35:29,080 WELL, THAT'S VERY INTERESTING. 2771 01:35:29,080 --> 01:35:30,440 I'LL HAVE TO LEARN ABOUT THIS 2772 01:35:30,440 --> 01:35:31,760 PRUDENT DIET AT SOME POINT. 2773 01:35:31,760 --> 01:35:32,480 DR. HOLLAND, DO YOU HAVE 2774 01:35:32,480 --> 01:35:35,000 ANYTHING TO ADD TO THAT? 2775 01:35:35,000 --> 01:35:36,120 >> AS LONG AS THERE'S COFFEE IN 2776 01:35:36,120 --> 01:35:38,800 THE DIET, I DON'T REALLY CARE. 2777 01:35:38,800 --> 01:35:41,400 SO I THINK WHAT WE'VE -- I DON'T 2778 01:35:41,400 --> 01:35:42,760 KNOW ANYTHING ABOUT THE 2779 01:35:42,760 --> 01:35:46,800 SPECIFICS OF THE DIFFERENT 2780 01:35:46,800 --> 01:35:47,800 DIETS, BUT THE WORK BEING DONE 2781 01:35:47,800 --> 01:35:51,360 OVER THE LAST DECADE OR SO IN 2782 01:35:51,360 --> 01:35:54,400 MICROBIOME HAS REALLY SHOWN A 2783 01:35:54,400 --> 01:35:55,840 PROFOUND EFFECT OF DIET ON 2784 01:35:55,840 --> 01:35:59,520 MICROBES AND MICROBES ON 2785 01:35:59,520 --> 01:36:01,920 IMMUNITY, EVERYTHING FROM IMMUNE 2786 01:36:01,920 --> 01:36:04,400 REACTIVITY TO CANCER. 2787 01:36:04,400 --> 01:36:06,720 AND I THINK IT'S REALLY HARD TO 2788 01:36:06,720 --> 01:36:09,200 SORT THOSE TWO APART, AND 2789 01:36:09,200 --> 01:36:10,360 CERTAINLY I LOOK FORWARD TO IT 2790 01:36:10,360 --> 01:36:17,040 BEING WORKED OUT MORE CLEARLY. 2791 01:36:17,040 --> 01:36:18,640 BUT I THINK WE SHOULD BE HUMBLE 2792 01:36:18,640 --> 01:36:20,040 ABOUT THE FACT THAT WHAT WE 2793 01:36:20,040 --> 01:36:22,840 CONSUME CLEARLY ACTIVATES OUR 2794 01:36:22,840 --> 01:36:24,520 COMPONENTS, WHETHER IT'S ABOUT 2795 01:36:24,520 --> 01:36:29,640 LACTOSE OR LACK TASTE LACTASE OR DIFFEREN T 2796 01:36:29,640 --> 01:36:30,640 BACTERIA, AND THOSE ARE 2797 01:36:30,640 --> 01:36:31,720 COMPLICATED STUDIES TO DO 2798 01:36:31,720 --> 01:36:33,200 BECAUSE THERE'S SO MUCH BACTERIA 2799 01:36:33,200 --> 01:36:35,240 IN THE ENVIRONMENT AND SO ON. 2800 01:36:35,240 --> 01:36:36,760 BUT THEY'RE CRITICALLY IMPORTANT 2801 01:36:36,760 --> 01:36:39,480 STUDIES TO DO, AND I THINK OUR 2802 01:36:39,480 --> 01:36:41,120 INSTITUTE AND MANY OTHERS ARE 2803 01:36:41,120 --> 01:36:43,080 REALLY COMMITTED TO TRYING TO 2804 01:36:43,080 --> 01:36:45,960 DISSECT OUT THOSE RELATIONSHIPS. 2805 01:36:45,960 --> 01:36:47,440 >> STEVE, I'M SO GLAD YOU 2806 01:36:47,440 --> 01:36:49,800 MENTIONED THE MICROBIOME AND IT 2807 01:36:49,800 --> 01:36:50,840 REMINDS ME ALSO THERE'S SOME 2808 01:36:50,840 --> 01:36:52,000 INTERESTING WORK FOR EXAMPLE 2809 01:36:52,000 --> 01:36:54,240 RELATED TO THE TREATMENT OF 2810 01:36:54,240 --> 01:36:56,880 RHEUMATOID ARTHRITIS AND 2811 01:36:56,880 --> 01:36:59,160 METHOTREXATE IS A DRUG WHERE THE 2812 01:36:59,160 --> 01:37:01,280 MICROBIOME INFLUENCES METABOLISM 2813 01:37:01,280 --> 01:37:03,840 OF THE DRUGS TOO, SO THAT'S 2814 01:37:03,840 --> 01:37:04,400 ANOTHER COMPLICATING FACTOR. 2815 01:37:04,400 --> 01:37:06,000 SO I AGREE THAT'S A REALLY RICH 2816 01:37:06,000 --> 01:37:07,320 AREA FOR FUTURE RESEARCH. 2817 01:37:07,320 --> 01:37:08,240 >> YEAH. 2818 01:37:08,240 --> 01:37:11,160 I MEAN, LIKE SO MANY THINGS, 2819 01:37:11,160 --> 01:37:12,160 IT'S SOMETHING THAT WE TOOK 2820 01:37:12,160 --> 01:37:13,880 LARGELY FOR GRANTED. 2821 01:37:13,880 --> 01:37:15,200 WE ASSUMED THAT YOU WERE PASSING 2822 01:37:15,200 --> 01:37:16,520 THAT STUFF OUT, IT WASN'T OUR 2823 01:37:16,520 --> 01:37:17,040 PROBLEM. 2824 01:37:17,040 --> 01:37:18,840 WELL, WE WERE WRONG. 2825 01:37:18,840 --> 01:37:20,240 SO IT WILL KEEP US BUSY FOR 2826 01:37:20,240 --> 01:37:23,400 QUITE A WHILE. 2827 01:37:23,400 --> 01:37:24,400 >> YES INDEED. 2828 01:37:24,400 --> 01:37:28,120 SO HERE'S A QUESTION FOR 2829 01:37:28,120 --> 01:37:29,000 DR. CRISWELL. 2830 01:37:29,000 --> 01:37:31,120 SORT OF HARKENING BACK TO HER 2831 01:37:31,120 --> 01:37:31,480 TALK. 2832 01:37:31,480 --> 01:37:33,640 ARE TWINS WHICH BOTH HAVE LUPUS 2833 01:37:33,640 --> 01:37:35,360 MORE PRONE TO HAVE THE SAME 2834 01:37:35,360 --> 01:37:36,680 CLINICAL MANIFESTATIONS THAN 2835 01:37:36,680 --> 01:37:40,160 RANDOM LUPUS PATIENTS? 2836 01:37:40,160 --> 01:37:42,840 >> THAT'S AN INTERESTING 2837 01:37:42,840 --> 01:37:43,240 QUESTION. 2838 01:37:43,240 --> 01:37:44,760 AS YOU CAN IMAGINE, THERE AREN'T 2839 01:37:44,760 --> 01:37:48,640 A LOT OF LARGE TWIN STUDIES IN 2840 01:37:48,640 --> 01:37:51,240 LUPUS, BUT SMALL STUDIES THAT 2841 01:37:51,240 --> 01:37:52,920 EXIST SUGGEST THAT THERE IS NOT 2842 01:37:52,920 --> 01:37:56,240 A LOT OF CONCORDANCE IN TERMS OF 2843 01:37:56,240 --> 01:37:59,240 THE SPECIFIC DISEASE 2844 01:37:59,240 --> 01:38:00,080 MANIFESTATIONS AMONG LUPUS 2845 01:38:00,080 --> 01:38:01,880 TWINS. 2846 01:38:01,880 --> 01:38:05,160 SO YOU MIGHT EXPECT THAT THE 2847 01:38:05,160 --> 01:38:06,360 DISEASE FEATURES WOULD BE VERY, 2848 01:38:06,360 --> 01:38:11,040 VERY SIMILAR, BUT THEY AREN'T AS 2849 01:38:11,040 --> 01:38:12,160 SIMILAR AS ONE MIGHT EXPECT, 2850 01:38:12,160 --> 01:38:13,840 WHICH ONCE AGAIN POINTS TO 2851 01:38:13,840 --> 01:38:14,840 EPIGENETIC FACTORS AND 2852 01:38:14,840 --> 01:38:15,840 EPIGENETIC DIFFERENCES BETWEEN 2853 01:38:15,840 --> 01:38:17,120 TWINS WILL INCREASE OVER THE 2854 01:38:17,120 --> 01:38:19,880 COURSE OF THEIR LIFETIME WITH 2855 01:38:19,880 --> 01:38:24,440 TIME, OR DIFFERENCES IN 2856 01:38:24,440 --> 01:38:25,960 EXPOSURES, CHANCE EVENTS, THAT 2857 01:38:25,960 --> 01:38:27,480 PROBABLY PLAYS AN IMPORTANT ROLE 2858 01:38:27,480 --> 01:38:28,640 TOO. 2859 01:38:28,640 --> 01:38:29,840 SO IT'S AN INTERESTING QUESTION. 2860 01:38:29,840 --> 01:38:31,280 THANKS FOR POSING THAT. 2861 01:38:31,280 --> 01:38:34,280 >> YEAH, AND YOU MENTIONED THE 2862 01:38:34,280 --> 01:38:37,360 QUESTION OF EPIGENETIC 2863 01:38:37,360 --> 01:38:37,840 EXPOSURES. 2864 01:38:37,840 --> 01:38:39,800 I KNOW THAT CIGARETTE SMOKING 2865 01:38:39,800 --> 01:38:42,280 HAS BEEN IMPLICATED AT LEAST IN 2866 01:38:42,280 --> 01:38:43,240 SOME AUTOIMMUNE DISEASES. 2867 01:38:43,240 --> 01:38:46,680 WITH THE DECREASE IN CIGARETTE 2868 01:38:46,680 --> 01:38:49,440 SMOKING IN THE GENERAL 2869 01:38:49,440 --> 01:38:50,360 POPULATION, HAS THERE BEEN ANY 2870 01:38:50,360 --> 01:38:51,680 CHANGE IN FREQUENCY OF 2871 01:38:51,680 --> 01:38:53,000 AUTOIMMUNE DISEASE, AT LEAST AS 2872 01:38:53,000 --> 01:38:55,640 OF YET? 2873 01:38:55,640 --> 01:38:58,080 >> I THINK ONE OF THE STRONGEST 2874 01:38:58,080 --> 01:39:00,600 ASSOCIATIONS FOR SMOKING IN 2875 01:39:00,600 --> 01:39:01,840 AUTOIMMUNE DISEASE IS PROBABLY 2876 01:39:01,840 --> 01:39:03,800 RHEUMATOID ARTHRITIS, WHERE THE 2877 01:39:03,800 --> 01:39:06,240 LUNG AND EXPOSURES THROUGH THE 2878 01:39:06,240 --> 01:39:07,680 LUNG INCLUDING CIGARETTE SMOKERS 2879 01:39:07,680 --> 01:39:09,000 ARE REALLY IMPORTANT IN TERMS OF 2880 01:39:09,000 --> 01:39:11,400 TRIGGERING THE DISEASE AND 2881 01:39:11,400 --> 01:39:13,000 CONTRIBUTING TO DISEASE 2882 01:39:13,000 --> 01:39:13,640 MANIFESTATIONS, AND THAT 2883 01:39:13,640 --> 01:39:16,280 PROBABLY EXPLAINS SOME OF THE 2884 01:39:16,280 --> 01:39:18,440 VARIATION IN RISK AROUND THE 2885 01:39:18,440 --> 01:39:19,920 WORLD, BUT THERE'S SO MUCH ELSE 2886 01:39:19,920 --> 01:39:21,080 THAT CONTRIBUTE TO THE DISEASE, 2887 01:39:21,080 --> 01:39:23,120 I THINK IT'S HARD TO 2888 01:39:23,120 --> 01:39:24,240 DEFINITIVELY SAY. 2889 01:39:24,240 --> 01:39:27,240 BUT CLEARLY SMOKING IS A MAJOR 2890 01:39:27,240 --> 01:39:29,600 CONTRIBUTOR TO RHEUMATOID 2891 01:39:29,600 --> 01:39:29,840 ARTHRITIS. 2892 01:39:29,840 --> 01:39:30,600 IT'S ALSO BEEN ASSOCIATED WITH 2893 01:39:30,600 --> 01:39:36,480 DOUBLE STRANDED DNA AUTO BODY -- 2894 01:39:36,480 --> 01:39:37,080 IN LUPUS. 2895 01:39:37,080 --> 01:39:39,440 AND THERE'S SOME OTHER SIMILAR 2896 01:39:39,440 --> 01:39:41,400 SORTS OF EXPOSURES. 2897 01:39:41,400 --> 01:39:43,200 PROXIMITY TO MAJOR HIGHWAYS HAS 2898 01:39:43,200 --> 01:39:46,440 BEEN ASSOCIATED WITH RISK OF 2899 01:39:46,440 --> 01:39:47,960 AUTOIMMUNE DISEASES INCLUDING 2900 01:39:47,960 --> 01:39:49,160 RHEUMATOID ARTHRITIS AS WELL, SO 2901 01:39:49,160 --> 01:39:51,040 THE PARTICULATE POLLUTION PLAYS 2902 01:39:51,040 --> 01:39:52,920 A ROLE. 2903 01:39:52,920 --> 01:39:55,160 >> JUST MAJOR HIGHWAYS IN 2904 01:39:55,160 --> 01:39:56,240 GENERAL, NOT SOME PARTICULAR 2905 01:39:56,240 --> 01:39:58,760 MAJOR HIGHWAY. 2906 01:39:58,760 --> 01:40:00,480 >> THE ONE CLOSEST TO YOUR 2907 01:40:00,480 --> 01:40:03,960 HOUSE, DAN. 2908 01:40:03,960 --> 01:40:05,720 THERE'S SOME REALLY COOL STUDIES 2909 01:40:05,720 --> 01:40:07,400 THAT LOOK AT DISTANCE TO MAJOR 2910 01:40:07,400 --> 01:40:08,720 ROADWAYS AND IT HAS DEMONSTRATED 2911 01:40:08,720 --> 01:40:09,680 STRONG ASSOCIATION. 2912 01:40:09,680 --> 01:40:12,200 >> MY GOODNESS. 2913 01:40:12,200 --> 01:40:13,280 ALL RIGHT. 2914 01:40:13,280 --> 01:40:14,640 WELL, HERE'S ONE FOR 2915 01:40:14,640 --> 01:40:15,000 DR. HOLLAND. 2916 01:40:15,000 --> 01:40:19,000 HAVE YOU LOOKED AT ANY 2917 01:40:19,000 --> 01:40:21,400 CORRELATION BETWEEN ANCYTOKINE 2918 01:40:21,400 --> 01:40:24,240 ANTIBODIES AND LONG COVID? 2919 01:40:24,240 --> 01:40:26,000 CAN IT BE USED AS A PREDICTOR OF 2920 01:40:26,000 --> 01:40:27,760 DISEASE AS PATIENTS ARE ADMITTED 2921 01:40:27,760 --> 01:40:29,720 TO HOSPITAL WITH COVID? 2922 01:40:29,720 --> 01:40:35,160 >> ASK ME IN A COUPLE OF MONTHS. 2923 01:40:35,160 --> 01:40:36,040 >> ALL RIGHT. 2924 01:40:36,040 --> 01:40:36,560 WELL, WE WILL. 2925 01:40:36,560 --> 01:40:37,200 OKAY. 2926 01:40:37,200 --> 01:40:41,440 SO LET'S SEE. 2927 01:40:41,440 --> 01:40:43,800 HERE IS ONE THAT PROBABLY COULD 2928 01:40:43,800 --> 01:40:46,520 BE ADDRESSED BY EITHER 2929 01:40:46,520 --> 01:40:50,600 DR. HOLLAND OR DR. CRISWELL. 2930 01:40:50,600 --> 01:40:52,000 CAN YOU COMMENT ON RECEIPT 2931 01:40:52,000 --> 01:40:53,720 LAITION RISK OR BENEFIT BETWEEN 2932 01:40:53,720 --> 01:40:55,800 LUPUS AND OTHER AUTOIMMUNE 2933 01:40:55,800 --> 01:41:07,000 DISEASES AND COVID VACCINATION? 2934 01:41:07,000 --> 01:41:08,840 >> IF YOU HAVE AN AUTOIMMUNE 2935 01:41:08,840 --> 01:41:09,920 DISEASE, IT'S IMPORTANT TO 2936 01:41:09,920 --> 01:41:11,000 RECEIVE A VACCINATION. 2937 01:41:11,000 --> 01:41:12,400 THERE ARE COHORT STUDIES THAT 2938 01:41:12,400 --> 01:41:14,240 ARE LOOKING AT VACCINATION 2939 01:41:14,240 --> 01:41:16,200 RESPONSE, WHICH OF COURSE CAN BE 2940 01:41:16,200 --> 01:41:18,440 DIMINISHED IN THE SETTING OF 2941 01:41:18,440 --> 01:41:20,360 TREATMENT AND IMMUNOSUPPRESSION. 2942 01:41:20,360 --> 01:41:23,160 SO THAT'S ONE OF THE CHALLENGES 2943 01:41:23,160 --> 01:41:25,000 ASSOCIATED WITH AUTOIMMUNE 2944 01:41:25,000 --> 01:41:28,480 DISEASE AND IMMUNOSUPPRESSANT IS 2945 01:41:28,480 --> 01:41:30,960 THE CORY SPONS TO 2946 01:41:30,960 --> 01:41:33,680 THE CORE RESPONSE TO 2947 01:41:33,680 --> 01:41:34,240 VACCINATION. 2948 01:41:34,240 --> 01:41:35,200 UNLESS ABLE TO SPEAK TO 2949 01:41:35,200 --> 01:41:37,200 DIFFERENCES IN ADVERSE EVENTS, 2950 01:41:37,200 --> 01:41:38,560 FOR EXAMPLE, AMONG LARGE NUMBERS 2951 01:41:38,560 --> 01:41:39,920 OF VACCINATED INDIVIDUALS WHO DO 2952 01:41:39,920 --> 01:41:41,520 AND DON'T HAVE AUTOIMMUNE 2953 01:41:41,520 --> 01:41:42,600 DISEASE, STEVE IS PROBABLY IN A 2954 01:41:42,600 --> 01:41:43,760 BETTER POSITION TO ANSWER THAT 2955 01:41:43,760 --> 01:41:43,920 ONE. 2956 01:41:43,920 --> 01:41:46,640 >> I DON'T THINK I'VE SEEN TOO 2957 01:41:46,640 --> 01:41:50,240 MUCH THAT SUGGESTS TO ME THAT 2958 01:41:50,240 --> 01:41:53,440 DISEASES LIKE LUPUS ARE BEING 2959 01:41:53,440 --> 01:41:55,200 EXACERBATED BY VACCINATION. 2960 01:41:55,200 --> 01:42:00,200 IN CONTRAST, I THINK MOST PEOPLE 2961 01:42:00,200 --> 01:42:02,680 THAT HAVE SORT OF TWITCHY IMMUNE 2962 01:42:02,680 --> 01:42:05,840 RESPONSES IN GENERAL GET INTO A 2963 01:42:05,840 --> 01:42:07,240 LOT MORE TROUBLE WITH INFECTION 2964 01:42:07,240 --> 01:42:08,360 THAN THEY GET WITH THE VACCINE. 2965 01:42:08,360 --> 01:42:09,920 THERE'S NO QUESTION THE VACCINE 2966 01:42:09,920 --> 01:42:11,240 IS AN IMMUNE ACTIVATOR, AND 2967 01:42:11,240 --> 01:42:12,240 THERE'S NO QUESTION THAT PEOPLE 2968 01:42:12,240 --> 01:42:15,480 FEEL LOUSY AND ALL THAT STUFF, 2969 01:42:15,480 --> 01:42:17,360 WHICH IS EVIDENCE THAT IT'S 2970 01:42:17,360 --> 01:42:17,920 WORKING. 2971 01:42:17,920 --> 01:42:23,760 BUT THE VIRUS INFECTION CAN 2972 01:42:23,760 --> 01:42:25,600 REALLY TRIGGER MUCH MORE SEVERE 2973 01:42:25,600 --> 01:42:26,040 REACTIONS. 2974 01:42:26,040 --> 01:42:27,400 I THINK THAT STUDY FROM THE 2975 01:42:27,400 --> 01:42:28,840 GROUP AT SAN FRANCISCO THAT WAS 2976 01:42:28,840 --> 01:42:31,920 THE LAST DATA SLIDE I SHOWED 2977 01:42:31,920 --> 01:42:34,280 SUGGESTS THAT THIS INFECTION, 2978 01:42:34,280 --> 01:42:37,160 THAT THE VIRUS INFECTION CAN 2979 01:42:37,160 --> 01:42:40,400 TRIGGER QUITE A BIT OF AUTO I 2980 01:42:40,400 --> 01:42:45,280 MAWN YOU 2981 01:42:45,280 --> 01:42:46,200 AUTOIMMUNE REACTIVITY. 2982 01:42:46,200 --> 01:42:48,680 THE QUESTION OF WHICH ONE DOES 2983 01:42:48,680 --> 01:42:49,920 IT TRIGGER, WHICH ONE PERSISTS 2984 01:42:49,920 --> 01:42:51,640 AND WHICH ONE BECOMES MORE 2985 01:42:51,640 --> 01:42:52,720 SYMPTOMATIC, THAT'S A MUCH MORE 2986 01:42:52,720 --> 01:42:54,240 COMPLEX QUESTION AND WHAT WE'RE 2987 01:42:54,240 --> 01:42:56,480 TRYING TO DO IS LOOK IN LONG 2988 01:42:56,480 --> 01:43:00,520 TERM PATIENTS TO SEE EXACTLY 2989 01:43:00,520 --> 01:43:01,920 WHICH AUTO ANTIBODIES ARE COMING 2990 01:43:01,920 --> 01:43:02,240 UP. 2991 01:43:02,240 --> 01:43:08,000 I DON'T THINK IT WILL BE AROUND 2992 01:43:08,000 --> 01:43:13,000 THE AUTO INTERFERON AUTO 2993 01:43:13,000 --> 01:43:13,600 ANTIBODIES, BUT THESE ARE ALL 2994 01:43:13,600 --> 01:43:15,560 GOING TO BE IMPORTANT FACTORS IN 2995 01:43:15,560 --> 01:43:18,160 SOME OF THE LONG-TERM SEQUELAE 2996 01:43:18,160 --> 01:43:20,000 OF COVID-19. 2997 01:43:20,000 --> 01:43:23,320 >> YES, YES, YES, I THINK THAT'S 2998 01:43:23,320 --> 01:43:24,680 A VERY GOOD POINT. 2999 01:43:24,680 --> 01:43:27,200 AND GOING BACK TO JENNIFER'S 3000 01:43:27,200 --> 01:43:29,640 STORY, IF I'M REMEMBERING 3001 01:43:29,640 --> 01:43:31,120 CORRECTLY, A YEAR BEFORE SHE WAS 3002 01:43:31,120 --> 01:43:33,360 DIAGNOSED WITH LUPUS, SHE HAD 3003 01:43:33,360 --> 01:43:36,280 CHICKEN POX, I GUESS IT WAS. 3004 01:43:36,280 --> 01:43:39,240 SO THERE, A VIRAL INFECTION, NOT 3005 01:43:39,240 --> 01:43:43,440 THAT SHE RECEIVED A VACCINE A 3006 01:43:43,440 --> 01:43:44,800 YEAR BEFORE DEVELOPING LUPUS. 3007 01:43:44,800 --> 01:43:47,040 BUT CERTAINLY THAT'S AN 3008 01:43:47,040 --> 01:43:48,200 IMPORTANT POINT, AND JUST THE 3009 01:43:48,200 --> 01:43:51,840 WHOLE IDEA OF THE TYPE 3010 01:43:51,840 --> 01:43:55,000 AND DEGREE OF STIMULATION OF THE 3011 01:43:55,000 --> 01:43:57,560 IMMUNE SYSTEM THAT MIGHT BE 3012 01:43:57,560 --> 01:43:58,960 ASSOCIATED WITH THE DEVELOPMENT 3013 01:43:58,960 --> 01:44:01,200 OF AN AUTOIMMUNE DISEASE. 3014 01:44:01,200 --> 01:44:01,400 OKAY. 3015 01:44:01,400 --> 01:44:07,400 SO NOW WE HAVE -- WE JUST HAVE A 3016 01:44:07,400 --> 01:44:14,560 WHOLE BUNCH OF QUESTIONS HERE. 3017 01:44:14,560 --> 01:44:14,840 HERE'S ONE. 3018 01:44:14,840 --> 01:44:16,520 IS THERE ANY EVIDENCE FOR 3019 01:44:16,520 --> 01:44:23,720 CERTAIN VIRUSES TRIGGERING 3020 01:44:23,720 --> 01:44:24,440 GASTROINTESTINAL INFLAMMATORY 3021 01:44:24,440 --> 01:44:25,640 DISEASES LIKE CROHN'S DISEASE? 3022 01:44:25,640 --> 01:44:26,960 SO WOULD THERE BE ANY EVIDENCE 3023 01:44:26,960 --> 01:44:28,920 THAT VIRUSES -- NOW OF COURSE 3024 01:44:28,920 --> 01:44:32,520 CROHN'S DISEASE IS MAYBE NOT 3025 01:44:32,520 --> 01:44:37,040 EXACTLY IN THE CATEGORY OF 3026 01:44:37,040 --> 01:44:38,160 LUPUS, BUT ANY THOUGHTS WITH 3027 01:44:38,160 --> 01:44:42,280 REGARD TO ENVIRONMENTAL EXPOSURE 3028 01:44:42,280 --> 01:44:48,640 IN CROHN'S DISEASE? 3029 01:44:48,640 --> 01:44:51,760 >> I WOULD JUST SAY FOR CROHN'S, 3030 01:44:51,760 --> 01:44:53,440 IF WE LUMP INFLAMMATORY BOWEL 3031 01:44:53,440 --> 01:44:54,240 DISEASE TOGETHER, IS THERE 3032 01:44:54,240 --> 01:44:56,200 EVIDENCE FOR INFECTIONS BEING 3033 01:44:56,200 --> 01:44:58,840 IMPORTANT TRIGGERS? 3034 01:44:58,840 --> 01:44:59,080 OH, YEAH. 3035 01:44:59,080 --> 01:45:00,760 I THINK THE EVIDENCE IS MUCH 3036 01:45:00,760 --> 01:45:02,480 STRONGER FOR ULCERATIVE COLITIS 3037 01:45:02,480 --> 01:45:06,280 THAN FOR CROHN'S, BUT THE 3038 01:45:06,280 --> 01:45:09,160 EVIDENCE FOR MICROBIOME EFFECT, 3039 01:45:09,160 --> 01:45:10,720 THE EVIDENCE FOR CHANGES IN 3040 01:45:10,720 --> 01:45:13,240 INFLAMMATORY BOWEL DISEASE RATES 3041 01:45:13,240 --> 01:45:18,000 BY LOCATION, IS VERY, VERY 3042 01:45:18,000 --> 01:45:18,240 STRONG. 3043 01:45:18,240 --> 01:45:19,520 NOW IT GETS CONFUSING AS WE WERE 3044 01:45:19,520 --> 01:45:27,040 TALKING ABOUT EARLIER, WE'VE GOT 3045 01:45:27,040 --> 01:45:28,000 VARIABLES ALL BEING MOVED AROUND 3046 01:45:28,000 --> 01:45:32,000 ET AROUND 3047 01:45:32,000 --> 01:45:33,080 AT THE SAME TIME. 3048 01:45:33,080 --> 01:45:37,320 PATHOGENIC MICROBES, COMMENSAL 3049 01:45:37,320 --> 01:45:38,600 MICROBES, VIRUSES, ALL OF THESE 3050 01:45:38,600 --> 01:45:40,440 ARE HAPPENING IN ALL OF US ALL 3051 01:45:40,440 --> 01:45:41,680 THE TIME, SO TRYING TO SORT OUT 3052 01:45:41,680 --> 01:45:44,800 WHICH ONE IS THE CAUSAL ONE IS 3053 01:45:44,800 --> 01:45:46,360 HARD, BUT I WOULD -- I THINK 3054 01:45:46,360 --> 01:45:47,880 THAT WE'D ALL AGREE THAT 3055 01:45:47,880 --> 01:45:50,840 ENVIRONMENTAL INFLUENCES ARE 3056 01:45:50,840 --> 01:45:51,400 CRITICALLY IMPORTANT IN THE 3057 01:45:51,400 --> 01:45:53,560 RATES OF INFLAMMATORY BOWEL 3058 01:45:53,560 --> 01:45:54,680 DISEASE, AND WHAT EXACTLY IT IS 3059 01:45:54,680 --> 01:45:58,840 THAT'S BEEN CHANGING OVER THE 3060 01:45:58,840 --> 01:46:02,920 LAST 50 YEARS, THE RATES OF 3061 01:46:02,920 --> 01:46:05,480 INFLAMMATORY BOWEL DISEASE AT 3062 01:46:05,480 --> 01:46:07,000 LEAST IN THE WESTERN WORLD WENT 3063 01:46:07,000 --> 01:46:08,200 THROUGH THE ROOF. 3064 01:46:08,200 --> 01:46:11,600 THAT'S NOT AN EVOLUTIONARY 3065 01:46:11,600 --> 01:46:12,560 EFFECT, THAT'S AN ENVIRONMENTAL 3066 01:46:12,560 --> 01:46:13,080 EFFECT. 3067 01:46:13,080 --> 01:46:14,200 BUT WHICH ENVIRONMENTAL EFFECT, 3068 01:46:14,200 --> 01:46:14,840 I'M NOT SURE YET. 3069 01:46:14,840 --> 01:46:15,840 >> ALL RIGHT, WELL, THANK YOU 3070 01:46:15,840 --> 01:46:16,240 FOR THAT. 3071 01:46:16,240 --> 01:46:16,720 OKAY. 3072 01:46:16,720 --> 01:46:19,240 SO NOW WE HAVE A QUESTION COMING 3073 01:46:19,240 --> 01:46:21,000 BACK TO JENNIFER, IF SHE'S READY 3074 01:46:21,000 --> 01:46:22,160 FOR TAKING ANOTHER QUESTION 3075 01:46:22,160 --> 01:46:27,000 HERE. 3076 01:46:27,000 --> 01:46:28,520 SO THE INTERROGATOR FIRST THANKS 3077 01:46:28,520 --> 01:46:29,600 YOU FOR SHARING YOUR STORY. 3078 01:46:29,600 --> 01:46:32,240 DO YOU HAVE SUGGESTIONS FOR HOW 3079 01:46:32,240 --> 01:46:37,360 WE CAN DO, WE AS HEALTHCARE 3080 01:46:37,360 --> 01:46:39,280 PROVIDERS CAN DO A BETTER JOB 3081 01:46:39,280 --> 01:46:40,240 COMMUNICATING THE RESEARCH 3082 01:46:40,240 --> 01:46:40,800 OPPORTUNITIES AVAILABLE FOR 3083 01:46:40,800 --> 01:46:41,040 PATIENTS. 3084 01:46:41,040 --> 01:46:42,880 IT SOUNDS LIKE YOU ARE AN 3085 01:46:42,880 --> 01:46:44,120 EDUCATED CONSUMER BUT THERE ARE 3086 01:46:44,120 --> 01:46:47,000 MANY WHO DO NOT UNDERSTAND HOW 3087 01:46:47,000 --> 01:46:48,000 TO NAVIGATE CLINICAL TRIALS AND 3088 01:46:48,000 --> 01:46:53,480 RESEARCH OPPORTUNITIES. 3089 01:46:53,480 --> 01:46:55,240 >> I WILL SAY I'VE CERTAINLY 3090 01:46:55,240 --> 01:46:56,520 BECOME AN EDUCATED CONSUMER, BUT 3091 01:46:56,520 --> 01:47:03,840 IT IS MY -- I MAKE A LIVING 3092 01:47:03,840 --> 01:47:07,840 TRANSLATING CLINICAL CONTENT 3093 01:47:07,840 --> 01:47:09,080 INTO PLAIN LANGUAGE. 3094 01:47:09,080 --> 01:47:10,840 IT SHOULD BE DONE, PERIOD. 3095 01:47:10,840 --> 01:47:18,120 ESPECIALLY IF YOU WANT TO REACH 3096 01:47:18,120 --> 01:47:19,800 PATIENTS. 3097 01:47:19,800 --> 01:47:21,080 I THINK HAVING INFORMATION COME 3098 01:47:21,080 --> 01:47:23,000 FROM A TRUSTED SOURCE IS A HUGE 3099 01:47:23,000 --> 01:47:24,480 ADVANTAGE, AND THAT CAN BE FROM, 3100 01:47:24,480 --> 01:47:27,320 FOR EXAMPLE, HOW I ENROLLED IN 3101 01:47:27,320 --> 01:47:29,200 DR. CRISWELL'S STUDIES, MY 3102 01:47:29,200 --> 01:47:30,080 RHEUMATOLOGIST SUGGESTED THAT. 3103 01:47:30,080 --> 01:47:33,960 SO UTILIZING A NETWORK OF 3104 01:47:33,960 --> 01:47:36,400 PROVIDERS TO SUPPORT RESEARCH 3105 01:47:36,400 --> 01:47:37,200 AND ENCOURAGE PATIENTS. 3106 01:47:37,200 --> 01:47:38,640 ANOTHER WAY TO DO THAT WOULD BE 3107 01:47:38,640 --> 01:47:40,840 THROUGH PATIENT ADVISORY GROUPS. 3108 01:47:40,840 --> 01:47:43,080 I SEE A LOT OF RECRUITMENT 3109 01:47:43,080 --> 01:47:48,840 HAPPENING NOW VIA SOCIAL MEDIA, 3110 01:47:48,840 --> 01:47:53,440 FACEBOOK, ET CETERA, THOSE WERE 3111 01:47:53,440 --> 01:47:54,080 DIRECT MAIL CAMPAIGNS. 3112 01:47:54,080 --> 01:47:58,440 THAT WAS HIGHLY IMPERSONABLE. 3113 01:47:58,440 --> 01:47:59,640 MY FAVORITE RECRUITMENT TACTIC 3114 01:47:59,640 --> 01:48:04,240 IS TO HAVE ENROLLED PATIENTS GO 3115 01:48:04,240 --> 01:48:09,560 OUT AND SPEAK TO A FRIEND WHO 3116 01:48:09,560 --> 01:48:12,480 HAS LUPUS OR MAYBE THROUGH A 3117 01:48:12,480 --> 01:48:15,000 CHURCH GROUP, PEOPLE WHO ARE 3118 01:48:15,000 --> 01:48:15,920 TRUSTED WHETHER IT'S SOMEONE 3119 01:48:15,920 --> 01:48:19,080 WITH A CONDITION OR SOMEONE IN 3120 01:48:19,080 --> 01:48:20,360 THE COMMUNITY, AND I KNOW BACK 3121 01:48:20,360 --> 01:48:22,000 WHEN DR. CRISWELL AND I WERE 3122 01:48:22,000 --> 01:48:24,920 WORKING TOGETHER, WE SPENT A LOT 3123 01:48:24,920 --> 01:48:26,560 OF TIME IN SMALL TOWNS AROUND 3124 01:48:26,560 --> 01:48:28,080 THE COUNTRY GOING TO LOCAL 3125 01:48:28,080 --> 01:48:29,480 SUPPORT GROUPS SO THAT PEOPLE 3126 01:48:29,480 --> 01:48:32,000 COULD MEET HER FACE-TO-FACE, ASK 3127 01:48:32,000 --> 01:48:33,360 QUESTIONS, AND THEN WE WOULD 3128 01:48:33,360 --> 01:48:34,640 ENROLL THOSE WHO ARE INTERESTED. 3129 01:48:34,640 --> 01:48:37,760 SO I THINK TRUST STILL REMAINS 3130 01:48:37,760 --> 01:48:41,160 SORT OF THE FOUNDATION FOR A 3131 01:48:41,160 --> 01:48:43,040 ROBUST ENROLLMENT CAMPAIGN. 3132 01:48:43,040 --> 01:48:43,400 >> ABSOLUTELY. 3133 01:48:43,400 --> 01:48:45,240 THANK YOU FOR THAT VERY 3134 01:48:45,240 --> 01:48:49,200 INSIGHTFUL COMMENT. 3135 01:48:49,200 --> 01:48:52,240 SO HERE'S A VERY HARD NOSED, 3136 01:48:52,240 --> 01:48:54,400 TOUGH QUESTION FOR DR. CRISWELL. 3137 01:48:54,400 --> 01:48:56,840 WHY IS IT USEFUL TO HAVE A 3138 01:48:56,840 --> 01:48:59,160 BLANKET DIAGNOSIS OF LUPUS GIVEN 3139 01:48:59,160 --> 01:49:02,760 THE HETEROGENEITY IN GENETIC AND 3140 01:49:02,760 --> 01:49:05,440 EPIGENETIC ETIOLOGY IN CLINICAL 3141 01:49:05,440 --> 01:49:06,120 MANIFESTATIONS? 3142 01:49:06,120 --> 01:49:07,360 WHY EVEN USE THE WORD LUPUS 3143 01:49:07,360 --> 01:49:07,760 ANYMORE? 3144 01:49:07,760 --> 01:49:09,560 THAT'S WHAT THE QUESTIONER WANTS 3145 01:49:09,560 --> 01:49:11,000 TO KNOW. 3146 01:49:11,000 --> 01:49:12,040 >> YEAH, THAT'S -- YOU KNOW, 3147 01:49:12,040 --> 01:49:13,760 THAT'S A GREAT QUESTION AND 3148 01:49:13,760 --> 01:49:15,520 THERE'S THIS PHRASE, ARE YOU A 3149 01:49:15,520 --> 01:49:18,120 LUM PER OR A SPLITTER. 3150 01:49:18,120 --> 01:49:19,680 SO THAT'S DEFINITELY LUMPING AS 3151 01:49:19,680 --> 01:49:20,560 OPPOSED TO SPLITTING. 3152 01:49:20,560 --> 01:49:23,480 SO MY HOPE IS THAT WITH GREATER 3153 01:49:23,480 --> 01:49:24,800 UNDERSTANDING OF THE UNDERLYING 3154 01:49:24,800 --> 01:49:27,360 CAUSES, WE CAN SPLIT INTO 3155 01:49:27,360 --> 01:49:29,040 HOMOGENEOUS SUBSETS. 3156 01:49:29,040 --> 01:49:31,080 AND THAT'S AN OVERARCHING GOAL 3157 01:49:31,080 --> 01:49:36,400 OF ETIOLOGICAL STUDIES, JE NE TI 3158 01:49:36,400 --> 01:49:37,240 GENETICS, EPIGENETICS. 3159 01:49:37,240 --> 01:49:40,760 TO THE EXTENT THOSE ARE -- 3160 01:49:40,760 --> 01:49:41,640 BIOLOGY, THAT'S GOT TO BE 3161 01:49:41,640 --> 01:49:43,160 RELATED TO THERAPEUTIC 3162 01:49:43,160 --> 01:49:44,480 APPROACHES, RESPONSE TO 3163 01:49:44,480 --> 01:49:47,800 TREATMENTS, OUT COME. 3164 01:49:47,800 --> 01:49:50,640 BUT THESE ARE -- MOST HUMAN 3165 01:49:50,640 --> 01:49:51,240 DISEASES ARE COMPLEX. 3166 01:49:51,240 --> 01:49:55,240 IT IS REALLY DIFFICULT TO DEFINE 3167 01:49:55,240 --> 01:49:56,920 THE APPROPRIATE ETIOLOGIC GROUP 3168 01:49:56,920 --> 01:49:58,400 WHEN YOU'RE TALKING ABOUT A 3169 01:49:58,400 --> 01:49:59,000 COMPLEX DISEASE. 3170 01:49:59,000 --> 01:50:00,120 NOW YOU'RE TALKING ABOUT A 3171 01:50:00,120 --> 01:50:03,840 SINGLE GENE DISORDER WITH 100% 3172 01:50:03,840 --> 01:50:05,200 PENETRANCE, THAT'S ONE THING. 3173 01:50:05,200 --> 01:50:07,240 BUT GARDEN VARIETY LUPUS IS VERY 3174 01:50:07,240 --> 01:50:09,400 DIFFERENT. 3175 01:50:09,400 --> 01:50:14,000 SO THESE CRITERIA EXIST BECAUSE 3176 01:50:14,000 --> 01:50:15,200 THERE'S A LOT OF CORRELATION 3177 01:50:15,200 --> 01:50:16,680 WITHIN INDIVIDUALS IN THESE 3178 01:50:16,680 --> 01:50:18,200 MANIFESTATIONS, SO THEY SEEM TO 3179 01:50:18,200 --> 01:50:19,400 CO-OCCUR, THEY CO-OCCUR IN 3180 01:50:19,400 --> 01:50:21,960 FAMILIES BS SO THEY'RE RELATED, 3181 01:50:21,960 --> 01:50:23,720 AND THERE ARE SOME SIMILARITIES 3182 01:50:23,720 --> 01:50:28,000 IN RESPONSE TO THERAPEUTIC 3183 01:50:28,000 --> 01:50:30,160 APPROACHES ACROSS FOLKS WITH 3184 01:50:30,160 --> 01:50:31,440 THESE DIFFERENT MANIFESTATIONS. 3185 01:50:31,440 --> 01:50:32,200 BUT I APPRECIATE THE QUESTION 3186 01:50:32,200 --> 01:50:34,680 BECAUSE I THINK WHERE WE NEED TO 3187 01:50:34,680 --> 01:50:36,760 GET IS A GREATER UNDERSTANDING 3188 01:50:36,760 --> 01:50:40,600 OF THE MOLECULAR BASIS AND 3189 01:50:40,600 --> 01:50:41,800 BETTER DEFINITIONS OF DISEASE 3190 01:50:41,800 --> 01:50:44,440 THAT RELATE TO THERAPIES. 3191 01:50:44,440 --> 01:50:46,640 >> IF I MAY JUMP IN, I JUST WANT 3192 01:50:46,640 --> 01:50:48,440 TO SAY THAT WHAT DR. CRISWELL 3193 01:50:48,440 --> 01:50:51,440 JUST SAID, IF WE CAN GET THERE, 3194 01:50:51,440 --> 01:50:53,560 IT WOULD AVOID SITUATIONS LIKE 3195 01:50:53,560 --> 01:50:58,560 THE ONE I EXPERIENCED, WHERE, 3196 01:50:58,560 --> 01:50:59,640 WE'LL KNOW IN A YEAR WHETHER 3197 01:50:59,640 --> 01:51:00,480 YOU'LL MAKE IT OR NOT. 3198 01:51:00,480 --> 01:51:02,320 THAT KIND OF UNKNOWN, EVERYONE 3199 01:51:02,320 --> 01:51:05,080 FALLS IN ONE BUCKET, I HOPE THAT 3200 01:51:05,080 --> 01:51:08,240 WE CAN GET THERE AND I THINK 3201 01:51:08,240 --> 01:51:10,240 FROM A PATIENT EXPERIENCE 3202 01:51:10,240 --> 01:51:11,560 STANDPOINT, I THINK THERE ARE 3203 01:51:11,560 --> 01:51:12,360 DISTINCT ADVANTAGES TO 3204 01:51:12,360 --> 01:51:16,840 CONTINUING DOWN THE PATH OF 3205 01:51:16,840 --> 01:51:17,560 UNDERSTANDING WHAT BUCKETS 3206 01:51:17,560 --> 01:51:18,520 EXIST. 3207 01:51:18,520 --> 01:51:22,320 >> SO THAT MAYBE 10 YEARS FROM 3208 01:51:22,320 --> 01:51:23,600 NOW, 20 YEARS FROM NOW OR 3209 01:51:23,600 --> 01:51:24,560 WHATEVER, WE'D BE ABLE TO SPLIT 3210 01:51:24,560 --> 01:51:26,280 A LITTLE BIT, ANYWAY, RATHER 3211 01:51:26,280 --> 01:51:29,640 THAN LUMP EVERYTHING. 3212 01:51:29,640 --> 01:51:30,920 THAT'S WHAT YOU'RE INTENDING TO 3213 01:51:30,920 --> 01:51:31,360 SAY, IS THAT RIGHT? 3214 01:51:31,360 --> 01:51:34,000 >> I WOULD CERTAINLY HOPE SO. 3215 01:51:34,000 --> 01:51:37,120 >> AND CERTAINLY, THERE'S EVERY 3216 01:51:37,120 --> 01:51:38,520 REASON TO BELIEVE GIVEN ALL THE 3217 01:51:38,520 --> 01:51:39,760 THINGS THAT YOU GUYS HAVE TALKED 3218 01:51:39,760 --> 01:51:44,400 ABOUT THAT THERE WILL BE 3219 01:51:44,400 --> 01:51:45,480 OPPORTUNITIES TO MAKE SOME OF 3220 01:51:45,480 --> 01:51:45,920 THOSE DISTINCTIONS. 3221 01:51:45,920 --> 01:51:47,480 SO HERE IS A QUESTION FOR 3222 01:51:47,480 --> 01:51:47,960 DR. HOLLAND. 3223 01:51:47,960 --> 01:51:51,080 AND THIS IS A QUESTION, I'M SURE 3224 01:51:51,080 --> 01:51:52,800 HE'LL TURN THIS RIGHT BACK ON 3225 01:51:52,800 --> 01:51:55,440 ME, BUT THIS IS A QUESTION FROM 3226 01:51:55,440 --> 01:51:57,440 MARK IN THE AUDIENCE, WHO WANTS 3227 01:51:57,440 --> 01:52:01,640 TO KNOW, DR. HOLLAND, IS THE IBS 3228 01:52:01,640 --> 01:52:03,880 DENSE 3229 01:52:03,880 --> 01:52:06,080 INCIDENCE OF ENVIRONMENTALLY 3230 01:52:06,080 --> 01:52:06,720 INDUCED REACTIONS DIFFERENT NOW 3231 01:52:06,720 --> 01:52:09,440 THAN, SAY, 150 YEARS AGO? 3232 01:52:09,440 --> 01:52:13,280 >> YOU KNOW, I WAS GOING BACK 3233 01:52:13,280 --> 01:52:15,000 THROUGH MY ROLODEX TO SEE WHAT I 3234 01:52:15,000 --> 01:52:17,960 WAS DOING ON THAT DAY, BUT I 3235 01:52:17,960 --> 01:52:21,640 THINK I LOOK PRETTY GOOD 3236 01:52:21,640 --> 01:52:23,520 ACTUALLY, BECAUSE YOU KNOW, I 3237 01:52:23,520 --> 01:52:29,240 THINK THIS IS A REALLY IMPORTANT 3238 01:52:29,240 --> 01:52:30,320 QUESTION, AND LET ME JUST SAY, 3239 01:52:30,320 --> 01:52:31,560 NUMBER ONE, I ACTUALLY WASN'T 3240 01:52:31,560 --> 01:52:33,400 THERE, BUT NUMBER TWO, THE 3241 01:52:33,400 --> 01:52:36,600 PROBLEM IS THAT WE'RE ONLY AS 3242 01:52:36,600 --> 01:52:37,680 GOOD AS THE RECORDS WE HAVE. 3243 01:52:37,680 --> 01:52:43,400 AND I THINK MOST OF US BELIEVE 3244 01:52:43,400 --> 01:52:47,720 THAT THINGS LIKE INFLAMMATORY 3245 01:52:47,720 --> 01:52:52,080 BOWEL DISEASE, ALLERGIES, PEANUT 3246 01:52:52,080 --> 01:52:53,200 ALLERGIES, I THINK MOST OF US 3247 01:52:53,200 --> 01:52:54,960 BELIEVE THOSE THINGS ARE 3248 01:52:54,960 --> 01:52:56,600 INCREASING IN FREQUENCY OVER THE 3249 01:52:56,600 --> 01:52:57,720 LAST FEW DECADES. 3250 01:52:57,720 --> 01:53:00,400 I REMEMBER I WAS AT A MEETING IN 3251 01:53:00,400 --> 01:53:06,640 ZAMBIA JUST A COUPLE YEARS AGO, 3252 01:53:06,640 --> 01:53:08,400 AND ONE OF THE IMMUNOLOGISTS 3253 01:53:08,400 --> 01:53:10,920 FROM ZIMBABWE WAS COMMENTING 3254 01:53:10,920 --> 01:53:11,720 OTHER THE FACT THAT OVER THE 3255 01:53:11,720 --> 01:53:13,200 LAST 10 YEARS, HE HAD SEEN 3256 01:53:13,200 --> 01:53:14,080 ALLERGIES TO THINGS HE HAD NEVER 3257 01:53:14,080 --> 01:53:16,040 SEEN ALLERGIES TO BEFORE. 3258 01:53:16,040 --> 01:53:20,080 PEANUTS, POTATOES, THINGS THAT 3259 01:53:20,080 --> 01:53:23,720 WERE STAPLES OF THE ZIMBABWE 3260 01:53:23,720 --> 01:53:25,160 DIET THAT HAD NOT BEEN CAUSING 3261 01:53:25,160 --> 01:53:26,440 TROUBLE UP UNTIL SOMETHING 3262 01:53:26,440 --> 01:53:27,040 CHANGED. 3263 01:53:27,040 --> 01:53:28,120 NOW WHAT THAT WAS, I DON'T KNOW 3264 01:53:28,120 --> 01:53:30,400 IF IT'S TOBACCO OR TWINKIES OR 3265 01:53:30,400 --> 01:53:31,440 WHAT, BUT IT'S SOMETHING THAT 3266 01:53:31,440 --> 01:53:34,240 WE'VE GOT HERE AS WELL. 3267 01:53:34,240 --> 01:53:39,240 SO I THINK THAT THE CHANGES OVER 3268 01:53:39,240 --> 01:53:41,040 THE LAST 150 YEARS ARE HARD TO 3269 01:53:41,040 --> 01:53:41,760 SORT OUT. 3270 01:53:41,760 --> 01:53:42,920 THE CHANGES OVER THE LAST 30 3271 01:53:42,920 --> 01:53:44,480 YEARS ARE EASIER TO SORT OUT, 3272 01:53:44,480 --> 01:53:45,640 AND THEY'RE QUITE DRAMATIC, AND 3273 01:53:45,640 --> 01:53:47,800 I THINK THIS IS WHERE WE'RE ALL 3274 01:53:47,800 --> 01:53:49,160 HAVING TROUBLE FIGURING OUT IS 3275 01:53:49,160 --> 01:53:52,440 THIS A MICROBIOME CHANGE, IS 3276 01:53:52,440 --> 01:53:53,640 THIS AN INGESTION CHANGE OR 3277 01:53:53,640 --> 01:53:54,800 MAYBE THOSE ARE ONE AND THE 3278 01:53:54,800 --> 01:53:55,280 SAME. 3279 01:53:55,280 --> 01:53:56,640 MAYBE IF YOU EAT A LOT OF 3280 01:53:56,640 --> 01:53:59,920 TWINKIES, YOUR MICROBIOME, MAYBE 3281 01:53:59,920 --> 01:54:01,840 IT'S TWINKED. 3282 01:54:01,840 --> 01:54:03,080 SO I THINK WE'RE ALL GOING TO 3283 01:54:03,080 --> 01:54:05,040 HAVE TO SORT OUT OVER THE NEXT 3284 01:54:05,040 --> 01:54:06,680 FEW YEARS EXACTLY WHAT ARE THOSE 3285 01:54:06,680 --> 01:54:08,800 EXPOSURES THAT ARE LEADING TO 3286 01:54:08,800 --> 01:54:09,000 THIS. 3287 01:54:09,000 --> 01:54:12,200 BUT IT'S CLEARLY ENVIRONMENTAL, 3288 01:54:12,200 --> 01:54:13,360 WE JUST DON'T KNOW WHICH PART OF 3289 01:54:13,360 --> 01:54:14,240 THE ENVIRONMENT IT IS. 3290 01:54:14,240 --> 01:54:16,760 >> THAT'S A VERY GOOD POINT. 3291 01:54:16,760 --> 01:54:19,920 VERY GOOD POINT. 3292 01:54:19,920 --> 01:54:20,880 SO I THINK WE'RE GETTING CLOSE 3293 01:54:20,880 --> 01:54:22,520 TO THE END HERE, BUT HERE'S A 3294 01:54:22,520 --> 01:54:28,120 GOOD QUESTION FOR DR. CRISWELL. 3295 01:54:28,120 --> 01:54:33,160 WHY IS THERE A PREDOM NAPTLY PREDOMINANTLY 3296 01:54:33,160 --> 01:54:33,920 FEMALE PREDISPOSITION TO DEVELOP 3297 01:54:33,920 --> 01:54:34,120 LUPUS? 3298 01:54:34,120 --> 01:54:35,720 >> YES, AND IT'S VERY STRIKING. 3299 01:54:35,720 --> 01:54:37,560 ONE OF THE MOST STRIKING AMONG 3300 01:54:37,560 --> 01:54:39,280 THE AUTOIMMUNE DISEASES. 3301 01:54:39,280 --> 01:54:40,520 AND THERE ARE SEVERAL LINES OF 3302 01:54:40,520 --> 01:54:44,080 EVIDENCE THAT IMPLICATE HORMONAL 3303 01:54:44,080 --> 01:54:49,280 FACTORS INCLUDING WHEN LUPUS 3304 01:54:49,280 --> 01:54:51,320 TENDS TO OCCUR OVER THE COURSE 3305 01:54:51,320 --> 01:54:54,240 OF THE LIFETIME IN RELATION TO 3306 01:54:54,240 --> 01:54:54,680 HORMONAL FACTORS. 3307 01:54:54,680 --> 01:54:56,880 THERE ARE GENES ON THE X 3308 01:54:56,880 --> 01:54:58,080 CHROMOSOME THAT HAVE BEEN 3309 01:54:58,080 --> 01:54:59,680 IMPLICATED IN LUPUS, BOTH FROM A 3310 01:54:59,680 --> 01:55:01,480 GENETIC STANDPOINT AN AN 3311 01:55:01,480 --> 01:55:02,440 EPIGENETIC STANDPOINT. 3312 01:55:02,440 --> 01:55:04,400 ALONG THOSE LINES, ONE OF THE 3313 01:55:04,400 --> 01:55:06,400 TYPES OF STUDIES THAT I FIND 3314 01:55:06,400 --> 01:55:09,520 MOST INTERESTING ARE STUDIES OF 3315 01:55:09,520 --> 01:55:15,520 FOLKS THAT HAVE ABNORMAL 3316 01:55:15,520 --> 01:55:16,840 KARYOTYPES, ABNORMAL SEX 3317 01:55:16,840 --> 01:55:17,560 CHROMOSOME STEREOTYPES. 3318 01:55:17,560 --> 01:55:20,440 FOR EXAMPLE, INDIVIDUALS WITH 3319 01:55:20,440 --> 01:55:23,000 TURNER SYNDROME, XO OR KLEIN 3320 01:55:23,000 --> 01:55:26,680 FELTER'S XXY, AND IN THOSE 3321 01:55:26,680 --> 01:55:28,000 INDIVIDUALS, THEIR RISK FOR 3322 01:55:28,000 --> 01:55:30,440 LUPUS RELATES TO THE NUMBER OF 3323 01:55:30,440 --> 01:55:32,360 COPIES OF THE X CHROMOSOME THEY 3324 01:55:32,360 --> 01:55:33,720 HAVE, NOT NECESSARILY THEIR 3325 01:55:33,720 --> 01:55:38,480 GENERAL PHENOTYPE. 3326 01:55:38,480 --> 01:55:41,240 SO KLEIN FELDER, MORE COMPARABLE 3327 01:55:41,240 --> 01:55:43,240 TO LUPUS, TURNER SYNDROME 3328 01:55:43,240 --> 01:55:46,480 FEMALES HAVE DECREASED RISK OF 3329 01:55:46,480 --> 01:55:47,760 LUPUS MORE SIMILAR TO MALES. 3330 01:55:47,760 --> 01:55:52,160 SO CLEARLY, TOESAGE OF GENES ON 3331 01:55:52,160 --> 01:55:54,040 THE X, WHETHER IT'S BECAUSE OF 3332 01:55:54,040 --> 01:55:58,480 INHERITANCE OF ADDITIONAL COPY 3333 01:55:58,480 --> 01:56:00,400 OF THE X OR PROBLEMS WITH X 3334 01:56:00,400 --> 01:56:02,320 CHROMOSOME INACTIVATION ARE PART 3335 01:56:02,320 --> 01:56:04,840 OF THAT EXPLANATION. 3336 01:56:04,840 --> 01:56:08,520 A TOUGHER QUESTION MIGHT BE 3337 01:56:08,520 --> 01:56:09,840 WHY -- NOT ALL AUTOIMMUNE 3338 01:56:09,840 --> 01:56:14,240 DISEASES SHOW THIS FEMALE 3339 01:56:14,240 --> 01:56:15,760 PREDISPOSITION, BUT ANYWAY, I 3340 01:56:15,760 --> 01:56:17,280 THINK BETWEEN HORMONAL FACTORS 3341 01:56:17,280 --> 01:56:19,760 AND GENES ON THE X CHROMOSOME 3342 01:56:19,760 --> 01:56:24,200 THAT GOES A LONG WAY TO EXPLAIN 3343 01:56:24,200 --> 01:56:25,520 THE FEMALE PREDOMINENCE FOR 3344 01:56:25,520 --> 01:56:25,720 LUPUS. 3345 01:56:25,720 --> 01:56:27,160 >> YES, INDEED. 3346 01:56:27,160 --> 01:56:30,840 WELL, AT THIS POINT, WE ARE DOWN 3347 01:56:30,840 --> 01:56:33,400 TO OUR LAST MINUTE AND 3348 01:56:33,400 --> 01:56:34,720 20 SECONDS OF THE TWO HOURS, AND 3349 01:56:34,720 --> 01:56:37,840 SO I THINK THAT AT THIS POINT, 3350 01:56:37,840 --> 01:56:38,960 WE SHOULD PROBABLY BRING THINGS 3351 01:56:38,960 --> 01:56:43,760 TO A CLOSE. 3352 01:56:43,760 --> 01:56:44,840 I AGAIN WANT TO THANK JENNIFER 3353 01:56:44,840 --> 01:56:46,120 FOR MAKING HERSELF AVAILABLE. 3354 01:56:46,120 --> 01:56:49,640 THIS HAS REALLY BEEN FANTASTIC, 3355 01:56:49,640 --> 01:56:51,280 HAVING THE VOICE OF A PATIENT 3356 01:56:51,280 --> 01:56:55,440 HERE TO REALLY PUT EVERYTHING IN 3357 01:56:55,440 --> 01:56:56,040 PERSPECTIVE. 3358 01:56:56,040 --> 01:56:58,520 I THANK DR. CRISWELL FOR A 3359 01:56:58,520 --> 01:57:00,240 WONDERFUL LECTURE AND 3360 01:57:00,240 --> 01:57:02,640 DR. HOLLAND FOR A WONDERFUL 3361 01:57:02,640 --> 01:57:05,160 LECTURE, AND ALL THREE FOR 3362 01:57:05,160 --> 01:57:06,840 ENTERTAINING QUESTIONS AND 3363 01:57:06,840 --> 01:57:12,360 REALLY BEING VERY NIMBLE IN 3364 01:57:12,360 --> 01:57:14,720 THEIR APPROACH TO ALL OF THE 3365 01:57:14,720 --> 01:57:15,440 DIFFERENT QUESTIONS THAT HAVE 3366 01:57:15,440 --> 01:57:16,240 BEEN POSED TO US. 3367 01:57:16,240 --> 01:57:17,840 SO WITH THAT, I THINK WE'LL CALL 3368 01:57:17,840 --> 01:57:19,240 TO A CLOSE. 3369 01:57:19,240 --> 01:57:21,240 THANK YOU AGAIN VERY, VERY MUCH. 3370 01:57:21,240 --> 01:57:24,520 THANK ALL OF THE PARTICIPANTS, 3371 01:57:24,520 --> 01:57:27,600 THE AUDIENCE, THE QUESTIONERS, 3372 01:57:27,600 --> 01:57:30,800 AND WE LOOK FORWARD TO A WHOLE 3373 01:57:30,800 --> 01:57:32,320 NEW AUDIENCE THAT WILL BE 3374 01:57:32,320 --> 01:57:34,800 VIEWING THIS OVER THE COURSE OF 3375 01:57:34,800 --> 01:57:37,040 THE NEXT WEEKS IN THE VIDEOCAST. 3376 01:57:37,040 --> 01:57:38,880 SO AGAIN, THANK YOU ALL VERY 3377 01:57:38,880 --> 01:57:39,280 MUCH. 3378 01:57:39,280 --> 01:57:40,640 HAVE A GOOD EVENING, 'ER ONE, 3379 01:57:40,640 --> 01:57:43,040 AND EVERYONE, 3380 01:57:43,040 --> 01:57:44,800 AND WE'LL LOOK FORWARD TO SEEING 3381 01:57:44,800 --> 01:57:46,120 EVERYONE BACK AGAIN NEXT TUESDAY 3382 01:57:46,120 --> 01:57:46,960 AFTERNOON. 3383 01:57:46,960 --> 01:57:47,240 THANK YOU. 3384 01:57:47,240 --> 01:57:53,400 >> AND THANK YOU, DAN. 3385 01:57:53,400 --> 01:58:09,600 >> BYE-BYE.