Cistanche txhim kho raum kab mob vim muaj kab mob Lupus Erythematosus

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

Rau Part 1, thov nias ntawm no.

Kev sib tham

Kev tawg ntawm kev kam rau siab tiv thaiv nuclear antigens yog lub cim ntawmkab ke lupuserythematosus, thiab ntxiv rau B hlwb, autoreactive T hlwb tau xav tias ua lub luag haujlwm tseem ceeb hauv nws cov kab mob. Txawm li cas los xij, raws li kev tshawb pom ntawm (auto) antigen-specificCD4^ntxiv T hlwb tseem ua rau muaj kev sib tw loj hauv kev tshawb fawb autoimmunity, txog niaj hnub no, me ntsis paub txog nuclear antigen-reactive CD4.^ntxivT cell hauvkab kelupuserythematosus.

Tsis ntev los no, cov txheej txheem tshiab rau kev kuaj pom thiab suav ntawm antigen-specific CD4^ntxivT hlwb tau tsim. Lub tsev qiv ntawv T-cell mus kom ze siv ua ntej kev nthuav dav polyclonal ntawm T hlwb kom pom tau tias tsis tshua muaj antigen tshwj xeeb T-cell clones. Cov tswv yim no muaj kev nkag siab zoo thiab tso cai rau kev ua haujlwm nrog cov hlwb tsawg. Siv cov txheej txheem no, peb muaj peev xwm ua kom pom cov T hlwb reactive tiv thaiv 5 canonical nuclear antigens nyob rau hauv cov neeg mob uas nquag nquag.kab kelupuserythematosus. Qhov tsis zoo ntawm kev tshawb nrhiav hauv tsev qiv ntawv yog, dhau li ntawm kev ua haujlwm hnyav, qhov kev loj hlob lossis poob ntawm qee qhov clones thaum lub sijhawm nthuav dav, theem tsis tuaj yeem raug cais tawm thiab cov kev txwv txwv rau kev tshuaj xyuas phenotypic ntawm cov hlwb.

Tus qauv cytometry yog txwv los ntawm tus naj npawb ntawm cov xwm txheej kuaj tau, uas feem ntau txwv tsis pub cov kev soj ntsuam ntawm cov qauv rau cov pej xeem nrog ntau zaus saum toj no 0.01 feem pua. Peb qhov kev soj ntsuam siv lub tsev qiv ntawv T-cell qhia tau hais tias qhov zaus ntawm circulating autoreactive CD4^ntxivT hlwb rau ib tug tshwj xeeb autoantigen nyob rau hauv cov neeg mob uas muaj tus kab mob flare yog w20 hlwb nyob rau hauv ib lab lub hlwb, sawv cev ib zaus ntawm 0.002 feem pua ​​; Yog li ntawd, kev kuaj pom ntawm autoantigen-specific CD4^ntxivT hlwb siv tus qauv, nonmanipulated khub cytometry yog yuav luag tsis yooj yim sua. Bacher et al. qhia ua ntej enrichment ntawm CD4^ntxivT hlwb uas reactive rau tej antigens ua ntej tau txais ntawm cov phooj ywg cytometry, hu ua ARTE txoj kev. Kev siv txoj hauv kev no rau kev tshawb pom ntawm nuclear antigen tshwj xeeb CD4^ntxivT hlwb, peb tuaj yeem lees paub peb qhov kev tshawb pom thiab ua kom pom qhov nthuav dav ntawm nuclear antigen-reactive CD4^ntxivT cells nyob rau hauv activekab kelupuserythematosus. Tshwj xeeb tshaj yog, zaus ntawm T hlwb reactive nrog transthyretin thiab C. Albicans yog indifferent ntawm kev noj qab nyob zoo tswj thiab cov neeg mob.kab kelupuserythematosusnrog cov kab mob sib txawv. Yog li ntawd, pom expansion ntawmautoreactiveT hlwbNws yuav tsis yog qhov tshwm sim ntawm kev ua haujlwm tsis ua haujlwmkab kelupuserythematosustab sis ntawm kev nthuav dav ntawm antigen tshwj xeeb T cells.

Covsystemic lupus erythematosuskis tus kab mobraum, yog li cistanche siv los tiv thaivlub raum.

Cov ntawv ceeb toom ua ntej twb tau qhia txog qhov muaj nyob ntawmautoreactiveT hlwbhauvkab kelupuserythematosus, feem ntau yog siv kev loj hlob, cytokine ntau lawm, los yog upregulation ntawm activation markers, txawm hais tias tsis muaj peev xwm txheeb xyuas qhov tseeb cov pej xeem ntawm cov hlwb. Cov ntaub ntawv pov thawj zoo tshaj plaws ntawm qhov zaus ntawm cov tshuaj tiv thaiv kab mob tshwj xeeb T-hlwb muaj nyob rau kev ua haujlwm tawm tsam U1 me ribonucleoprotein, tus yam ntxwv autoantigen lub hom phiaj hauv cov kab mob sib xyaw ua ke thiab pom tsuas yog nyob rau hauv ib feem ntawm cov neeg mob.kab kelupuserythematosus. U1 me me nuclear ribonucleoprotein- reactive CD4^ntxivT hlwb tau txiav txim siab los ntawm kev txwv qhov dilution thiab Enzyme-Linked Immuno Spot Assay (ELISPOT) thiab tau tshaj tawm tias tshwm sim ntawm ntau zaus (40 txog 250) 106 T hlwb thiab (20 txog 60) 106 PBMCs, raws li, uas yog qhov zoo sib xws. magnitude raws li qhov zaus ntawm autoreactive hlwb hauv peb txoj kev tshawb fawb. Hauv peb txoj haujlwm, peb tau tshawb xyuas qhov kev tawm tsam tawm tsam ntau tus yam ntxwvkab kelupuserythematosus-ssociated nuclear antigens. Interestingly, txawm hais tias tag nrho cov neeg mob uas nquag LN pom tau tias muaj ntau zaus ntawm anti-nuclear antigen-reactive CD4.^ntxivT hlwb, cov neeg mob sib txawv nyob rau hauv lawv cov hom phiaj portfolio, thiab lub reactivity yog aimed ntawm ib tug dav txheej ntawm antigens piv rau cov neeg mob uas inactive.kab kelupuserythematosus. Qhov tseem ceeb ntawm kev lom neeg ntawm qhov no yog tam sim no tsis paub. Sib txawv CD4^ntxivT cell reactivities tuaj yeem koom nrog qee qhov kev kho mob tshwm sim ntawm cov reactivities sib txawv uas tej zaum yuav rov ua dua rau tus kab mob pathogenesis.

Zoo ib yam li lwm yam kab mob autoimmune, peb kuj tuaj yeem ua kom pom qhov muaj nyob ntawm autoreactive CD4.^ntxivT hlwb hauv cov tib neeg noj qab haus huv, txawm tias tsawg zaus piv rau cov neeg mob uas muaj kab mob lupus erythematosus. Cov hlwb no tsis tuaj yeem kuaj pom los ntawm kev sib piv cov xov tooj ntawm tes ua haujlwm nrog lossis tsis muaj cov tshuaj tiv thaiv antigen, txawm tias muaj cov txheej txheem rhiab heev xws li T-cell qiv lossis ARTE txoj kev. Txawm li cas los xij, los ntawm ib leeg-cell cloning, peb muaj peev xwm ua kom pom tau tias "tom qab" teeb liab muaj autoantigen-specific CD4.^ntxivT hlwb. Cov xwm txheej tshwj xeeb twg ua rau kev ua siab ntev ntev thiab nce zaus ntawmautoreactiveT hlwbtseem speculative; Txawm li cas los xij, peb cov ntaub ntawv qhia tau hais tias kev nthuav dav ntawm autoreactive clones ua si ib feem hauv lub pathogenesis ntawm lub cev lupus erythematosus.

Circulating nuclear antigen-reactive CD4^ntxivT hlwb feem ntau tsim IFN-g thiab, rau qhov tsawg dua, IL-17 thiab IL-10. Qhov cytokine profile no ua ke nrog qhov tsis muaj zog / tsis muaj kev sib raug zoo nrog autoantibody ntau lawm qhia tias lub luag haujlwm ntawm nuclear antigen-reactive CD4^ntxivT cells yuav tsis yog tus muab kev pabcuam tshwjxeeb ntawm B cell. IFN-g tau pom tias yog qhov tseem ceeb hauv cov kab mob ntawm LN. Th1 hlwb tau pom tias tau txais neeg ua haujlwm rau hauvtau kis kab mob raumcev inkab ke lupuserythematosus, ua nuclear antigen-reactive T hlwb thawj cov neeg sib tw los txeeb covlub raum, qhov twg lawv yuav ntsib lawv cov cognate autoantigen ubiquitous. Urinary T hlwb tau piav qhia yav dhau los los cuam tshuam txog kev ua haujlwm ntawm cov kab mob thiab tsom iav qhov phenotype ntawm intrarenal hlwb hauv LN20,33; Yog li, peb siv cov urinary T cells ua tus tso cai rauraumT hlwb. Cov kab mob hauv zis tau qhia txog qhov txwv tsis pub TCR hloov pauv, uas yog nyob rau hauv txoj kab nrog kev soj ntsuam hauvraumbiopsies, qhia txog kev txhim kho ntawm qee yam T-cell clones hauv covtau kis kab mobraumntaub so ntswg. Ntawm cov urinary T cells, peb tuaj yeem kuaj pom cov tshuaj tua kab mob nuclear-reactive T cells, thiab lawv cov zaus tau nce ntxiv piv rau T hlwb. Yog li ntawd, nws zoo nkaus li hais tias cov kab mob nuclear-reactive hlwb ncaj qha koom rau hauv kev nthuav tawm ntawm lub cev puas tsuaj.

Hauv cov ntsiab lus, peb ntawm no qhia tau hais tias nuclear antigen-reactive CD4^ntxivT hlwb tau nthuav dav tsis ua haujlwmkab kelupuserythematosus; lawv yog phenotypically mas IFN-g-tsim Th1 T hlwb thiab ntxeem tautau kis kab moblub hom phiaj lub cev xws li covraum.

Cistanche tuaj yeem zam qhov kis kab mob mus rauraumvimkab kelupuserythematosus.

Txoj kev

Cov txheej txheem ntxaws ntxaws tau muab rau hauv Cov Khoom Siv Ntxiv.

Cov ntsiab lus thiab cov ntshav thiab zis kuaj

Cov ntshav kuaj tau los ntawm 17 tus neeg noj qab haus huv, 12 tus neeg mob tsis ua haujlwmkab kelupus erythematosus(kab kelupuserythematosusDAI qhab nia<10), and="" 20="" patients="" with="" active="">kab kelupuserythematosus(kab kelupuserythematosusDAI score >10). Tsis tas li ntawd, cov zis kuaj tau los ntawm 12 cov neeg mob uas muaj kev ua haujlwmkab kelupuserythematosusthiab LN. Txhua yam kev kawm tau muab lawv qhov kev tso cai pom zoo raws li kev pom zoo ntawm kev coj ncaj ncees uas tau txais los ntawm pawg thawj coj saib xyuas thiab kev coj ncaj ncees ntawm Charité - Universitätsmedizin Berlin (EA 1/342/12, EA 1/098/07, thiab EA 1/036/16). ). PBMCs thiab urinary cells tau npaj siv FicollHypaque density gradient.

Antibodies thiab ua raws li cytometry

Nyob ntawm qhov kev sim, ntau qhov chaw molecules tau stained ntawm antigen-stimulated hlwb nyob rau hauv sib txawv ua ke ntawm cov nram qab no monoclonal antibodies: anti-CD3, -CD4, -CD8, -CD14, -CD20, -CD69, thiab -CD154; txhawm rau cais cov hlwb nyob thiab tuag, cov khoom siv LIVE/DEAD Aqua (Life Technologies Ltd.,Paisystemiclupuserythematosus, UK) tau siv.

Txhawm rau stain lub intracellular cell compartment, cov hlwb raug kho nrog 2 feem pua ​​(v/v) paraformaldehyde rau 15 feeb ntawm chav tsev kub thiab permeabilized nrog BD FACS Permeabilizing Solution 2 (BD Biosciences, San Jose, CA); cov antigens hauv qab no tau stained intracellularly los ntawm kev siv tus qauv raws tu qauv: CD154, IFN-g, IL-2, IL-4, IL-10, thiab IL-17.

Cov qauv tau txais ntawm BD FACSCanto II thiab BD LSRFortessa (BD Biosciences) ua raws cytometers ntawm Flow Cytometry Core Facility Deutsches Rheuma-Forschungszentrum Berlin los ntawm kev siv BD FACSDiva software (BD Biosciences). Flow cytometry cov ntaub ntawv tau txheeb xyuas siv FlowJo software (FlowJo v10, Peb Lub Hnub Qub, Ashland, VA).

Antigen thiab antigen pool npaj

Peb siv cov antigens hauv qab no los txhawb CD4^ntxivT hlwb hauv cov tsev qiv ntawv T cell: {{0}}}.5 mg/ml ntawm tib neeg SNRPD1 (SmD1) recombinant protein (Biorbyt Ltd., Cambridge, UK), 50 ng/ml ntawm tib neeg SNRP70 (RNP70) recombinant protein (Abcam Plc., Cambridge, UK), 0.5 mg/ml ntawm natural human histone protein (Abcam Plc.), 0.5 mg/ml ntawm tib neeg SS -A/Ro recombinant protein (kev ua siab zoo muab los ntawm Euroimmun AG, Lübeck, Lub teb chaws Yelemees), 0.5 mg / ml ntawm tib neeg SS-B / La cov recombinant protein (kev siab zoo muab los ntawm Orgentec Diagnostika GmbH, Mainz, Lub teb chaws Yelemees), 1 mg / ml ntawm SEB (Sigma-Aldrich Chemie GmbH, Steinheim, Lub teb chaws Yelemees), 1 mg / ml ntawm PepTivator Candida albicans MP65 (Miltenyi Biotec GmbH, Bergisch Gladbach, Lub teb chaws Yelemees), thiab 0.5 mg / ml ntawm tib neeg transthyretin recombinant protein (ATGen, Seongnam, Kaus Lim Qab Teb ).

Peripheral thiab urinary T-cell cov tsev qiv ntawv Cov txheej txheem los tsim kom muaj cov khoom siv hauv peripheral thiab tso zis T-cell cov tsev qiv ntawv tau txais thiab hloov kho raws li tau piav qhia dhau los.14 Luv luv, 200, 000 peripheral CD4^ntxivT hlwb los yog 500 mus rau 2000 zis CD4^ntxivT hlwb raug cais los ntawm kev siv tshuaj tiv thaiv humanCD4^ntxivMicroBeads (Miltenyi Biotec GmbH) raws li cov chaw tsim khoom cov lus qhia. Lub purity ntawm CD4^ntxivT-cell feem yog niaj hnub tshuaj xyuas siv ua raws cytometry raws li CD3^ntxivCD4^ntxiv expression, where the purity always reached >99 feem pua ​​​​thiab 70 feem pua ​​​​rau 75 feem pua ​​​​rau cov ntshav peripheral thiab tso zis, feem. Nyob rau tib lub sijhawm, cov tshuaj antigen-presenting hlwb tau npaj los ntawm kev sau CD3 hlwb los ntawm PBMCs tom qab depletion nrog anti-tib neeg CD3 MicroBeads (Miltenyi Biotec GmbH) thiab cryopreserved. Tom qab 1 mus rau 2 lub lis piam ntawm kab lis kev cai, cov feem ntawm amplified CD4^ntxivT hlwb tau muab faib rau hauv 96- daim hlau zoo, nyob ntawm seb muaj pes tsawg tus antigens yuav raug tshuaj xyuas. Ua ntej stimulation nrog cov antigens, hlwb tau so tsawg kawg yog 4 hnub. Nyob rau hnub ntawm stimulation, antigen-tam sim no hlwb raug thawed thiab muab faib mus rau hauv lub T-cell kab lis kev cai nyob rau hauv ib tug ratio ntawm tsawg kawg yog 1 antigen-tam sim no cell rau 100 CD4.^ntxivT hlwb. CD4^ntxivT-cell cov tsev qiv ntawv rau kev tswj tsis zoo (cov hlwb tsis muaj zog) thiab kev tswj xyuas zoo (cov cell txhawb nqa nrog SEB) yeej ib txwm suav nrog hauv kev sim. CD4^ntxiv T hlwb tau txhawb nqa nrog cov antigen rau 4 hnub, thiab kev loj hlob tau txiav txim siab siv tus qauv [3 H]-thymidine raws tu qauv.

Amplified T-cell blasts teb txawv rau cov antigens tso tawm los ntawm heterogeneous scintillation CPM; Yog li, ib qho normalization ntawm qhov pib loj hlob tau txiav txim siab raws li tus neeg pub nyiaj tshwj xeeb z tau tsim nyog. Cov qhab nias z raug xam raws li 5 qhov sib txawv ntawm 75th thiab 25 feem pua ​​​​ntawm qhov nruab nrab CPM ntawm unstimulated microcultures. Cells hauv microcultures stimulated nrog SEB tau txais kev tswj hwm zoo. Nco ntsoov, microcultures nrog SEB stimulation Performance index ntawm<5 for="" peripheral="" blood="" samples,="" or="" 4="" for="" urinary="" samples,="" were="" excluded="" because="" it="" indicated="" poor="" cell="" viability.="" enumeration="" of="" the="" precursor="" frequency="" of="" antigen-specific="">^ntxivT hlwb tau suav nrog cov lej ntawm cov microcultures tsis zoo raws li Poisson faib thiab qhia txog 1 lab hlwb, raws li tau piav qhia yav dhau los. Kev siv Poisson faib yog raws li qhov tshwm sim uas tsawg kawg 1CD4^ntxivT cell yog tam sim no nyob rau hauv ib qho microculture ntawm T-cell cov tsev qiv ntawv thaum lub teeb liab xov tooj cua tau kuaj pom tom qab antigen tshwj xeeb stimulation.

Peripheral thiab tso zis ARTE txoj kev peb ua raws li cov txheej txheem uas siv CD154 MicroBead Kit (Miltenyi Biotec GmbH). Luv luv, cov hlwb raug txhawb rau 7 teev nrog antigens thiab tom qab ntawd sau nrog cov tshuaj tiv thaiv tib neeg CD154- biotin antibodies thiab anti-biotin microbeads raws li cov chaw tsim khoom cov lus qhia. Labeled hlwb raug thauj mus rau calibrated MS txhua (Miltenyi Biotec GmbH) kom txhawb CD154- qhia cov hlwb. Kev sau npe ntawm cov hlwb nrog carboxyfluorescein diacetate N-succinimidyl ester (Sigma-Aldrich Chemie GmbH) tau ua tiav raws li tus qauv txheej txheem.

Cistanche txhim khoraummuaj nuj nqi.

Generation ntawm ib leeg-cell clones

Ib leeg-cell clones tau tsim los ntawm antigen-reactive hlwb, uas tau enriched los ntawm CD154 qhia raws li ARTE raws tu qauv. CD154- nthuav tawm cov hlwb raug lim nrog 30- hli npaj lim (Miltenyi Biotec GmbH) thiab rov ua dua hauv 1 ml ntawm 20 feem pua ​​(v/v) txias phosphate-buffered saline, 0.5 feem pua ​​​​bovine serum albumin, thiab 2mM ethylenediaminetetraacetic acid. Cells yog ib lub hlwb cais rau CD154^ntxivcd69 ua^ntxivphenotype, thiab ib leeg sorted hlwb tau coj mus rau hauv ib lub qhov dej ntawm 96-zoo daim hlau nyob rau hauv lub xub ntiag ntawm feeder hlwb. Cell kab lis kev cai tau khaws cia li 3 mus rau 4 hnub kom txog thaum pom ob peb clones. Ib hnub ua ntej restimulation, antigen-tam sim no hlwb tau thawed thiab muab faib mus rau hauv T-cell kab lis kev cai nyob rau hauv ib tug ratio ntawm

tsawg kawg yog 1 antigen-kev nthuav qhia ntawm tes rau 100 CD4^ntxivT hlwb. Cells tau txhawb nqa nrog 1 mg / ml ntawm antigen, thiab unstimulated clones tau txais kev tswj tsis zoo.

Tom ntej no tsab xov xwm sequencing-based TCR repertoire tsom xam

Genomic DNA yog cais los ntawm peripheral CD4^ntxivT hlwb thiab cov zis tso zis siv AllPrep DNA/RNA Micro Kit (Qiagen, Venlo, Lub Netherlands). Recombined TCR-b locus tau nthuav dav raws li txoj cai raws li tau piav qhia dhau los. Cov ntawv nyeem tau ua tiav siv IMSEQ, thiab sib npaug clonotypes tau muab faib ua pawg thiab tshuaj xyuas ntxiv.

Kev txheeb cais

Cov ntawv xeem tau ua nrog GraphPad Prism software (Prism 8, GraphPad Software Inc., La Jolla, CA). Bonferroni hloov kho rau ntau qhov sib piv tau siv. Mann-Whitney U test thiab Wilcoxon kos npe-qib xeem tau siv nyob rau hauv kev sim nrog cov ntaub ntawv ywj pheej thiab nyob ntawm seb, raws li. Tom qab Bonferroni hloov kho rau ntau qhov kev sib piv, kev suav ntawm qhov tseem ceeb P qhov tseem ceeb tau raug kho vim nws yog raws li tus naj npawb ntawm kev sib piv. P tus nqi<0.01 were="" considered="" statistically="" significant="" with="" the="" following="" indication:="" *p="" <="" 0.01,="" **p="" <="" 0.005,="" and="" ***p="" <="" 0.0005.="" correlation="" analyses="" were="" performed="" using="" spearman="" rank="" correlations="" by="" showing="" the="" absolute="">kab kelupuserythematosusDAI qhov tseem ceeb es tsis txhob muab cov txiaj ntsig zoo los muab kev nkag siab zoo ntawm kev sib raug zoo ntawm cov xov tooj ntawm tes thiab kab mob. Rau kev txheeb xyuas kev sib raug zoo, P tus nqi<0.5 were="" considered="" statistically="" significant="" with="" the="" following="" indication:="" *p="" <="" 0.05,="" **p="" <="" 0.01,="" and="" ***p="" <="" 0.001.="" when="" background="" frequencies="" were="" higher="" than="" the="" frequencies="" of="" nuclear="" antigen–reactive="">^ntxivT hlwb, cov zaus tsis muaj keeb kwm yav dhau tau txhais tias yog xoom. Lub log (x þ 1) kev hloov pauv tau siv rau cov ntaub ntawv teev thaum nws suav nrog xoom qhov tseem ceeb. Cov ntaub ntawv ntxiv rau tus neeg mob thiab cov ntaub ntawv txheeb xyuas muaj nyob hauv Cov Lus Ntxiv S1 thiab S2.

Nuclear antigen-reactive CD4^ntxivhlwb nthuav dav hauv activekab kelupuserythematosus, tsim effector cytokines, thiab kis tus kab moblub raum, cistanche tuaj yeem tiv thaiv covlub raum.

Qhia tawm

Txhua tus kws sau ntawv tshaj tawm tsis muaj kev sib tw txaus siab.

TXOJ CAI

Peb ua tsaug rau Toralf Kaiser thiab Jenny Kirsch (Flow Cytometry thiab Cell Sorting Facility, Deutsches Rheuma-Forschungszentrum Berlin) rau kev pab nrog flflow cytometry thiab cell sorting. Kev them nyiaj yug rau cov kev tshawb fawb no yog muab los ntawm cov nyiaj pab los ntawm Deutsche Forschungsgemeinschaft nyob rau hauv Sonderforschungsbereich 650 rau GR thiab los ntawm cov nyiaj pab los ntawm Deutsche Gesellschaft für Nephrologie thiab Clinical Scientist Program ntawm Charité-Universitätsmedizin Berlin thiab Berlin Institute of Health rau PE.

SUPPLEMENTARY MATERIAL Supplementary File (PDF)

Daim duab S1. Autoreactive nuclear antigen tshwj xeeb CD4^ntxivT hlwb raug kuaj pom los ntawm T cell tsev qiv ntawv txoj kev. Daim duab S2. cd154 ua^ntxivcd69 ua^ntxivCD4^ntxivT hlwb cais tawm tom qab stimulation nrog nuclear antigens los ntawm cov neeg noj qab haus huv yog bona-fife antigen-specific CD4^ntxivT hlwb.

Daim duab S3. Cov zaus ntawm cytokine-tsim autoreactive CD4^ntxivT hlwb tau muab piv nrog cov titer ntawm antinuclear antibodies (anti-ANA) (A), thiab nrog cov concentration ntawm anti-ob strand DNA antibodies (anti-dsDNA) (B).

Daim duab S4. Nuclear antigen-reactive CD4^ntxivT hlwb raug kuaj pom nyob rau hauv cov zis ntawm activekab kelupuserythematosuscov neeg mob LN.

Tab S1. Cov ntaub ntawv kho mob.

Tab S2. Cov ntsiab lus ntawm cov nqi nruab nrab.

Cov txheej txheem ntxiv.

Ib zaug lubraumyog tus kab mob vim yog nuclear antigen-reactive CD4^ntxivcell expanding nyob rau hauv activekab kelupuserythematosus, covraumkev ua haujlwm raug rhuav tshem, cistanche yog siv los txhim khoraummuaj nuj nqi.

REFERENCES

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2. Arbuckle MR, McClain MT, Rubertone MV, et al. Kev loj hlob ntawm autoantibodies ua ntej qhov chaw kho mobkab kelupuserythematosus. N Engl J Med. 2003; 349: 1526–1533.

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4. Crow MK, DelGiudice-Asch G, Zehetbauer JB, et al. Autoantigen-specific T cell proliferation tshwm sim los ntawm ribosomal P2 protein nyob rau hauv cov neeg mob.kab kelupuserythematosus. J Clin Invest. 1994; 94:345–352.

5. Engler JB, Undeutsch R, Kloke L, et al. Unmasking ntawm autoreactive CD4^ntxivT hlwb los ntawm depletion ntawm CD25 tswj T cells nyob rau hauvkab kelupuserythematosus. Ann Rheum Dis. 2011; 70:2176–2183.

thiab lwm yam.