Reveille, John D., M.D.

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John D. Reveille, M.D. Professor and Director Division orRheumatology ·-··· -·- ---------· ····---·--University of Texas Health Science Center at Houston -·j·---i· Th~-.LP!'U~-AAIJlx-.a~w11-t~-§~~-$b,~..{;Lt¥-~ntth~~QW:~r---m~i m~ m~n Mf.! RW!t. Th~n tM ~mm §~!S!; ·,r nwrx, wh!!~ th~Y ~r~ 9,m~ RxRR!~, gl! ~R~g~!r.~ m~ l>,ijm~ lg!WHfl~~. th~¥ hf!Y~ imm~~ tQ f.!Q tni~, n9,m!n~ YX'!' ~tQR th~m ,~wr fmrn ~h1,1wv~r th~¥ Rr~s.~ni~ iR ~R, Lx1 H~ ~2 9,9,Yfn ~n~ lhxrn ~RnfH~x m~!r ,~niw~~!-'.· ~Q rh$Jt 9nx '«ill 119,} Hn.f.!mt1'n~ Yi'.hgt thx Rthxr ~loWf' ThH~ lh~ ~~RR ~s;~n~rnS! m~m rrnrnmiHx g!! 9,v~r m~ ~~rm, ?!1S! Wt¥ ~tRRR~S! RHHflin~ mf ~jty, Th~l i~ WhY it ':Y~§ s;!!l!x.S! ~g~~j,,," . Genesis 11: 5-9 -! · ·· · · ·· ·· ··' •. ,• ..... ,.,_ • The Epic of Gilgamesh depicts the adventures of the historical King Gilgamesh of Uruk in Babylonia. It dates to about 2700 BC and was originally written on 12 clay tablets in the cuneiform script of ancient Sumeria. • Gilgamesh's ancestor Ut-napishtim (who with his wife had been the only survivor of a great flood similar in many ways to the biblical account in Genesis) told him of a plant that gave eternal life. After obtaining the plant, however, Gilgamesh left it unguarded and a serpent carried it off. . 3000 3C 2500,BC . , 2i)OO BC 1.SOOBC preselllclay '-----~----..,.....---~~ i:epi_e.S.GlllaliYe INDO-EIJROPEAN Sl'EM 00' HITTFTE ~ROUP -------,---1 npne. , r : ·.t':"• ARYAN ·c· Ind~·. Hin.di.. · .:.' . ' l : · Iranian ' Fal'sL(Persianj " , ' .• . ~ .•.,. '.' , BALI0· -cB~tic Li\flu.apian · •: f EAST ' l· BALrD· ';(SlAVJC • Slal'ic P,o!l,h, Russilln IE , ,SLAVO• • ""'' ' . GERMANIC , GERMANIC -- Engl~h .. G'oifroM GRAECO· {GREEK --- • G.ree~ ' nlRACIAN IHAACO, --· - 'Armenian• . PHRYGlliN . . • ILLYRIAN . - . . ·.· . . . Albanian wm_P · · · ·· I.E •' "LGELTO--c· ITALIC~ f<enc/';11,i!ian.Spamsf. , · ITALIC · CEHQ: . {. · . .Celtic Welsh elGURIAN Ligurian no"!' ( :fooo B.C. ' l,-J·..,;...~ 83--~--□---·-· lil!i(:=:._-••;..~ '"~·=-· -=~---on mapNlO m, , world total 25 million) 8~ IUll!!ltm1i11111,_, ... , ........... ,,um111m ~~½t\?t~j!f :e ".' -::, ....... ..:. ........ .:.:..·· _:::..';:"--.r-•:'· ~ .. _,.,., { ···•"·· L_, ::_ .~ .. ~ ~ --- ~""'-::J. -~"';:;.-~ ~ 7~~--~~~~~~:~ _ .~- s~=:-:-. r::s:~. - ~---~ - · .,_ ,,..,., --__ ,.._,, __ 600A.D. The Peopling of America Current DNA studies support two, and possible three genetically distinct groups that settled the Americas: 1. the first, occurring up to 30,000 years ago (the Amerinds) comprised the groups in South and central America and Eastem North America 2. The second, occurring later, comprised the Pacific Northwest and Southwest tribes (Pima, Navajo )·the NaDenes. 3. A third group comprised the Eskimos ,J x Toll receptors x NOD proteins x Complementsystem x Phagocytosis x Cytoplasmic viral receptors x Antimicrobial peptides x Apoptosis P~!~~!Et\~ C9r.t1E9.Ng~T R;B~fL~CTIN~ Tt!~-lm:WE~~f THE 6,A,S.<l\.lf.$:1,...,,E,,__, ·--1 rr,1;~9,~ffH!~ MNf .. . .. . . . .. . 7 -· / '"/ -~-.;' .. ,./ R!ff§ij~~~~§ ~HW.§~N eRAPTIV~ ANR !NN8T~lM~!lNffY . - . . . ,. . -.... ' . Innate Adaptive Action time Early (hours) late (days) Cell types Macrophages, dendritic B, T lymphocytes cells, neutrophils Receptors Fixed in genome (I.e. toll Gene rearrangement necessary receptors) (i.e. B cell receptor, T cell receptor) Recognition Conserved molecular Wide variety of molecular Evolution pattem (i.e.LPS) structures (i.e. proteins, peptides-over 1 x 1018) Evolutionarily conserved Only vertebrates (plants, animals) n,...J.~.tlaMH~.Tho.l.6-Mb_t.OfC ,eOdaino~DlglQ•&dlodivid"'mobH-• Th•loc . lli1111ofc•~ .....tndinmigt11pn,ca1:1i,,g0f P1't1.-ii... "'" oh"'"'inblur on,1•,•mdusiul"' !IL,\. rn•(HLA:-£.•F'"'."-f3J" .. IM'ft>~gml'l..hrlyroapoi,1111soflHna,pltlunlcUC1dolCI.Cl.l'ropt1iliD ~~B)-•,t,_~'":"-DJ ...... ~H.;p.w,.djn.otnHro.ipmo•(HSPIJ"""l;MICAondM(CB)or11b>om --~•-~ T-Hoc:ni,uF_-r;r...,.ofg...(LT"-TMP',_..,4LTil)ifol,°'"'1llrod.Olbng .. or INCl!.•HOTCH ~A0ER. llOCll.21-0H-A 1111.S~!'SOR.SI ...SCDSN.v11bo-.ninyollVIII' • Group HLA-haplotype Advantage Disadvantage caucasians 8*08, C4A*QO, ?protection autoimmunity (Celts) DRB1*0301, against infection DQ81*0:Z01 Caucasians 8*07, DR81*1501, ?protection SLE, Multiple (Gen11anics) DQ81*060:Z against infection sclerosis, narcolepsy <;-'.> -• ... ; :; . - ~:. .. ~ .... :-;,,,,;,,,,. caucasians 8*2705, DR81*0101, Protection against Anky1osing DQ81*0501 viral infections spondylitis (HIV, infiuenza) .:i§iI~: . .-l•'WI ~'!-"'- l·L Africans 8*53, DR81 *1304 Protection against severe malaria East Asians DR81*0405, ?protection autoimmunity DQ81*0401 against infection 8§§RP!8TI~~§ Qf MH~ e~~~~~§ e~R 8~TQllYffffilfWRI§~~ ·-·---Subspeclalty Disease MHC Association Rheumatology Rheumatoid Arthritis DRBJ*04, ¥OJ, *1001 Systemic lupus erythematosus DR81*0301, *1501, C4A*QO Scleroderma DR81*11, DR81*1502 Ankylosing spondylltis 8*:27 Pulmonary Narcolepsy DQ81*060:Z Endocrinology Type I Diabetes Meflitus DQ81 *0201, DQ81*0302 Autoimmune thyroid Disease DRl/1 *0301, DQ81 *0201 Gastroenterology Cellac Disease DQB1 *02, DQ81 *0302 Neurology Multiple Sclerosis Df/81*1501, DQ81*0602 Myasthenia Gravis 8*08, DR81*0301 Dem,atology Dermatitis herpetiformls DR81 *0301, DQ81 *0201 tf ~d:~6§;~Q~8NR fl~eB~HNftl'HF-W~B~R--- ---DR4 subtype Linked DQB1 Associated allele with RA? Northern European *0401, *0404 *0301, *0302 Yes Caucasians Eastern European *0402 *0302 No Caucasians Spanish, Basques *0405 *0302 Yes North Africans *0404 •0202 Yes East Asians *0405 *0401 Yes East Asians *0406 *0302 No Native Americans *0407, *0411 *0302 No (Hispanics) FTHNIC R!Ff~RFNCF~ IN ~~F:~~§QCl8TFR 8~Tq8NTTijm~rg~~F~\:!J'x1li9-a-~QMPR 1 Autoantibody Hispanic (n=205) Texas Puerto Rico African- Caucasian N=110 N=95 American (n=163) P Value (n=208) ANA 100 95 99 99 0.020 Anti-dsDNA 71 51 60 38 <0.0001 nephritis Anti-Sm 8 13 25 9 <0.0001 Anti-RNP 32 25 50 30 <0.0001 Raynaud's, myositis aPL- 19 2 17 18 0.0014 thrombosis ~ " FcyRlla, Illa x PTPN22 nn.(lo Vun) ;;~5~:f:b + R62QW polymorphism-not seen in Asians and Afr. Americans x FCRL3 x CR2 x B lymphoid tyrosine kinase (BLK) and C8orf13 • Hom et al. N Engl J Med. 2008 Feb 28;358(9):900-9. x BANK1 x STAT4 " IRF5-seen in all ethnic groups x CD11b-x ideotified io ¾318 mdivictg,al~ of Euro~e~n dJlsl/:ffn~ an~ A'mggita~J~ento In epen en sample O In IVI ua S 0 9~!N!9A~ M~~Jrn~TN!RN~ 9F ~~~ !NTH~ F~Pf!t-~ ~T~QY ~y ~HN!~~~~: , Hispanic Afr American Caucasian p " CriteriQ□ (!'l=lQ9l (N=33~l (N=46Zl Vs!l~g x Malar rash 64% 45% 67% <0.0001 x Discoid rash 6% 33% 12% <0.0001 x Photosensitivity 59% 46% 72% <0.0001 x Renal involvement 59% 54% 23% <0.0001 x Serositis 64% 60% 42% <0.0001 x Cytopenias 85% 82% 62% <0.0001 x Immunologic 83% 79% 65% 0.0003 MHx ~~N~§ 1Mrk1cer~R J....,,N~--1( f~~R}~fR§!T!R~ TR §~~ + HLA-DRB1 *0301 in Caucasians + HLA-DRB1 *1501/*1503 implicated in Africans, Chinese, Japanese and some Caucasian cohorts + HLA-DRB1 *08 in Hispanics, secondary association in Caucacasians x HLA-DQA1, DQB1 + Associated primarily with autoantibody subsets of SLE x C4 null alleles (C4A *QO, C4BQ*0) x Susceptibility x Profiling severity and outcome x Identification of new targets for drug discovery x Pharmacogenomic profiling to predict response to therapy 

Genes, Ethnicity, and Autoimmunity: A Historical Perspective

https://openworks.mdanderson.org/context/dhaw/article/1062/filename/0/type/additional/viewcontent/Reveille.pdf

Genes, Ethnicity, and Autoimmunity: A Historical Perspective

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