Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. e zhang wei erythematosus aggravated lupus with systemic correlates cells CD27+IgD+B of Dysfunction onl,teefidnssgetta D7IDBcl yfnto oetal otiue oteeaebto fSE and SLE, CD27 of of disease. exacerbation persistent Dysfunction the this treating to for contributes tool potentially powerful restored. a dysfunction were represent amounts cell may cell CD27+IgD+B features CD27+IgD+B their that remission, modulating immunological SLE suggest and achieving findings clinical treatment with these effective correlations Here, terms Following Jointly, negative in showed patients. undefined. function also SLE remain altered cells had in SLE CD27+IgD+B cells in properties these production. Moreover, properties IgM functional amounts. antibody-like CD27+IgD+B cell their natural Human CD27+IgD+B However, of reduced producers. markedly ILBs. nIgM showed considered main SLE from are with the them individuals preventing cells) are and cells B au- cells (ILBs) memory of apoptotic of B- (un-switched biosynthesis clearing innate-like cells occurrence the in and important to Concurrent B-1- is leads autoimmunity. (SLE). (nIgM) which deleterious IgM erythematosus production, triggering Natural autoantigen lupus promotes disorders. systemic autoimmune phagocytosis and altered in toantibodies and disordered death obviously cell apoptotic is induced pathway signaling apoptotic The Abstract 2020 28, October 4 3 2 1 SE.Cnurn curneo nue ppoi eldahadatrdpaoyoi pro- erythematosus phagocytosis altered lupus and systemic death in cell disordered apoptotic induced obviously of is occurrence pathway Concurrent (SLE). signaling apoptotic The Peking Sciences, Pharmaceutical of Summary School Drugs, [email protected] Biomimetic e-mail, author’s and Corresponding Natural of China Laboratory Lab- Beijing, Key Key China. University, Beijing Beijing, State & (BZ0135), Hospital Diagnosis 4. People’s Immune University and Mechanism Peking Rheumatism Immunology, for and oratory Rheumatology of 014010 Department Autoimmunity, Immunol- of 3. of Laboratory Institute Key College, Mongolia Medical College,(Inner Baotou China) Medical of Baotou, Baotou hospital Rheumatology, affiliated and first ogy The Rheumatology, of Department University, Jiaotong 2. Xi’an Medicine, of School Hospital, Affiliated China Second Xi’an, he Laboratory,T Research Core 1. W Zhang, is ffiitdHsia fBoo eia College Medical Baotou of Hospital Affiliated First College Hospital Medical People’s Baotou University of Peking University Hospital Jiaotong Affiliated Xi’an First of the Hospital Affiliated Second The 1,2 1 ag YF Wang, ; oguWang Yongfu , + 2 u Fl Hu, ; IgD 2 + aliHu Fanlei , el orltswt grvtdssei uu erythematosus lupus systemic aggravated with correlates cells B 3,4 u FA Lu, ; 3 2 uilu fuai , u T Wu, ; 1 2 4 i K Li, ; a Wu Tao , 1* 4 n eLi Ke and , 1 Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. oal 0SEad5 elh oto H)ptet eeerle.Idvdaswt L eetetdin treated were SLE with Individuals enrolled. were patients (HC) control healthy 50 and SLE 50 Totally therapy. samples after tendency and their Patients revealed and associations Methods clinical and their Materials analyzed CD27 we of capacity addition, IgM-producing In antibody-like patients. natural and SLE amounts the determined we Here, CD27 However, perpetuation(11). encniee Lsi uas9.IB epntrlIMaonsa h taysae n ucl gain quickly and previous state, Our steady activation(10). the innate after at IL-10 amounts and CD27 IgM IgM indicated natural natural of study keep secretion via ILBs features humans(9). modulatory immune in ILBs considered been fayia el ossigint esn n epnigfaue.MueIB opieB- marginal group B1-, heterogeneous comprise CD19 a ILBs represent cells. Mouse ILBs B of features. hand, 80% related responding that other other and admitted the and sensing is On B- innate It (MZ) cells(8). possessing producers. zone B1 cells IgM by B natural atypical them produced main preventing of the is constitute and IgM cells natural cells (ILBs) serum apoptotic B- clearing innate-like and in B-1- development important found the very toward epitopes indeed tendency multiple autoimmunity. is the with triggering Natural increases nIgM reacting from deficiency humans, tolerance. disorders; nIgM in immune autoimmune it immunity Therefore, enhances Meanwhile, of innate antigens(7). and of non-self cells. part response self-and apoptotic critical inflammatory in and a of represents injured regulation (nIgM) of intricate IgM elimination the and performs identification NETosis also the and enables causes necrosis immunity and death, reactions individuals Natural immune cell addition, induces (programmed that In self-dsDNA death the 5). Cell of molecules, disorders(6). apoptosis(4, most autoimmune cells. provides signaling of NETs]), increase apoptotic is apoptotic via abnormal clearing neutrophils pathway (TWEAK) of [affecting to trouble signaling apoptosis leads number have of apoptosis ligand), SLE inducer large the (Fas weak with FasL a that TNF-like such ligand (TRAIL), of demonstrated death proto-oncogenes ligand been production and intracellular inducing has Abnormal apoptosis and It TNF-related Fas) SLE. including (e.g., in members(3). proteins family disordered surface Bax obviously unraveled(2). cell and remains by Bcl-2 SLE controlled immune- as in strictly and antibodies of is death role cell Apoptosis is exact programmed the It could However, reactions, Antibodies injury. unclear. inflammatory associated signs. complement-mediated remain pathological complexes SLE’s mechanisms via genetic of determinants with pathogenetic self-tissues main humans Its harm the affects represent disorder, autoantibodies conditions(1). that autoimmune environmental admitted systemic certain major in a susceptibility (SLE), erythematosus lupus for Systemic tool powerful a Introduction represent may features their Keywords: modulating disease. and persistent this SLE, treating of CD27 exacerbation that Fol- the suggest patients. CD27 SLE findings CD27 in these remission, properties Jointly, SLE production. immunological achieving IgM treatment and effective antibody-like clinical individuals lowing with natural Here, correlations of negative undefined. terms showed remain CD27 in SLE reduced function in markedly altered properties showed functional SLE their with However, ILBs. ered hmfo rgeigdltrosatimnt.B1 n naelk -(Ls el r the are cells (ILBs) preventing B- and innate-like CD27 cells and Human apoptotic B-1- clearing producers. autoim- in autoimmunity. nIgM and important deleterious main autoantibodies is triggering of (nIgM) from biosynthesis IgM them the Natural to disorders. leads mune which production, autoantigen motes ytmclpseyhmtss CD27 erythematosus, lupus systemic + IgD + elipimn nremti rhii R) ieycnrbtn odisease to contributing likely (RA), arthritis rheumatoid in impairment cell B + IgD + elpoete n ucini L eanundefined. remain SLE in function and properties cell B + IgD + + + CD27 + IgD + el u-wthdmmr el)aeconsid- are cells) B memory (un-switched cells B IgD IgD 2 + + + + eldsucinptnilycnrbtsto contributes potentially dysfunction cell B IgD elaons oevr hs el had cells these Moreover, amounts. cell B el,int-ieBcls,ntrlIgM natural , cells B innate-like cells, B + el o nwthdmmr el)have cells) B memory unswitched (or cells B + IgD + elaonswr restored. were amounts cell B + IgD + + IgD el also cells B + el in cells B Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. rncito a are u ihteRvrAdFrtSrn DAsnhsskt(emna,UA as USA) (Fermentas, kit synthesis and cDNA GAPDH Strand 2 assessment. qRT-PCR the First by and RevertAid followed normalization, manufacturer, the the with by out instructed carried CD27 was from transcription as extraction cytometer flow RNA II Total Aria FACS cells analysis a (qRT-PCR) target RT-PCR on the antibiotics real-time Next, 2% Quantitative purity). and (95–99% above. FBS manufacturer 10% described the containing as by (PBMC) 1640 directed staining cell RPMI mononuclear and in blood centrifugation collected peripheral by density-gradient were followed Ficoll patients, HC by CD27 and isolation SLE purify from to obtained utilized were was specimens (FACS) and sorting properties cell scatter Fluorescence-activated on based culture the excluded and and were sorting China) cells (MultiSciences, Dead Cell buffer II. lysis Aria FACS RBC a the staining. on with 7-AAD assessed out were carried (eBio- cells was anti-IgD remaining lysis FITC-labeled and erythrocyte USA) Then, (eBioscience, science). anti-CD27 APC-linked USA), (BioLegend, anti-CD19 oprdwt h 0idvdaswt L Fgr BadC). and 1B (Figure SLE CD27 with CD27 individuals circulatory higher 50 remarkably showed the HCs with 50 compared The patients. HC CD27 and of SLE between function the examine To ANOVA one-way P t-test, appropriate. as paired analysis t-test, statistical Student’s for significance. performed analysis. statistical were data respectively, indicated for correlation, employed rank was Spearman and USA) (SPSS, 17.0 SPSS analysis. data for utilized 10 was analysis brief, USA) Statistics Ltd., In Technology (Cellular Sweden). Analyzer AB, (3 ImmunoSpot anti-CD40 (MABTECH An with Kit incubation after IgM IgM Human for ELISpotPLUS with CD27 purified out carried was ELISPOT ELISPOT 100 post- immunosup- weeks CD27 4 administered For at 2 were Table and cases in treatment analysis summarized SLE to cytometry are prior All Flow post-treatment collected and Baotou were study. pre- of specimens follow-up features Board Patient Blood a Review treatment. remission. in Ethics disease assessed with Medical participant. (SLEDAI were pressants, each Institutional disease patients from the active obtained SLE and from was Twelve approval Disease n=34) consent informed (SLEDAI- 0-4, had 1. signed Table of Index trial and in (SLEDAI Activity This College, listed (LDA) Disease Medical are activity Erythematosus n=16). cases disease Lupus 4, SLE low Systemic the above as of modified Rheumatology classified features of and the main College 2K)(13), by American The measured the SLE(12). applied was of that activity classification College the Medical Baotou for of criteria Hospital Affiliated First the el eegopdit utpsacrigt D7adIDlvl,icuigna¨ıve including (CD27 levels, IgD and CD27 to according (CD27 subtypes 4 like into grouped were cells B patients SLE μ rs hl lo el a xrce n nuae ihtefloigantibodies:APC-CY7-labeled following the with incubated and extracted was cells blood whole fresh l + IgD + + IgD IgD + + elaonscreaewt lncladimnlgclfaue nSEpatients SLE in features immunological and clinical with correlate amounts cell B + IgD + ,sice eoy(CD27 memory switched ), eldtcin -lbodseieswr olce rmSEadH ains and patients, HC and SLE from collected were specimens blood 2-ml detection, cell B + el n te eltpsfo L n Cptet,rsetvl,wr assessed were respectively, patients, HC and SLE from types cell B other and cells B -ΔΔ῝Τ ehdwsapidfrdt analysis(11). data for applied was method ResultsCD27 + + IgD IgD + + el nSEptoeei,teraonswr rtycompared firstly were amounts their pathogenesis, SLE in cells B el tlzdRes iiKt(ign emn) Reverse Germany). (Qiagen, Kit Mini RNeasy utilized cells B μ /l Bocec)adCG(10 CpG and eBioscience) g/ml, + IgD + IgD - n obengtv (CD27 negative double and ) 3 + elaonsaesgicnl erae in decreased significantly are amounts cell B + IgD μ /l nioe,UA o 24h. for USA) Invivogen, g/ml, + el.Bifl,1-lblood 10-ml Briefly, cells. B - IgD β- ci eeepoe for employed were actin - el Fgr 1A). (Figure cells B ) + IgD + - elamounts cell B IgD + ,innate- ), < 0.05 4 Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. h bv nig ugse htCD27 that suggested findings above the nioylk g.I hssuy CD27 CD27 study, These this affinity. In low IgM. and antibody-like poly-reactivity (19). with SLE CD27 unknown. that human IgM largely demonstrated in remain we events patients study, cardiovascular SLE previous of in a defects frequency In anti-PC IgM higher decreased natural patients a addition, of In SLE with causes show in duration. associated the SLE IgM disease However, are with with natural Individuals amounts correlates of IgM blood(18). which amounts in natural reduction, Decreased accumulating level cells IgM IgM(17). other dead three- natural with of and are anti-PC clearance, absence MBL macrophages cell can that the IgM, apoptotic cells found in C1q, reduce have apoptotic might (SAP), phagocytic studies of component less Previous Phagocytosis P four-fold mechanism. amyloid to backup materials. redundant serum bridging but a (CRP), forming phagocytes, and/or protein macrophages) proteins, functional opsonins C-reactive on (e.g., by as only increased cells acting not be proteins depends phagocytic clearance patho- soluble professional autoimmune cell SLE on by and apoptotic in also However, phagocytosis factor production conditions. undergo occur- major autoantibody normal Concurrent a cells under subsequent represents 15). Apoptotic and phagocytosis impaired(14, accumulation deficient is disorders(16). and autoantigen phagocytosis death while promoting cell increases genesis, apoptotic cells increased apoptotic con- of of healthy rence number with the compared SLE, SLE In treatment. with effective patients by restored in were IgM and CD27 antibody-like addition, natural In of trols. production CD27 the that regarding revealed study current The after activity disease in Discussion reduction significant a treatment. had effective by cases all SLEDAI, the CD27 meanwhile, by 4B); (Figure levels measured treatment platelet As and 4A). leukocyte were Total (Figure amounts protein degree. CD27 certain urinary a 24h Next, to and disease normalization anti-dsDNA decreased level addition, post-treatment. markedly C4 In heightened and treatment were C3 expected, 2). serum (Table As assessed with SLEDAI were reduced, initiation. the SLE post-treatment on with weeks based diagnosed previously activity 4 patients and 12 Totally relapse during assessed. was treatment effective following CD27 ascertain To CD27 for ability CD27 that SLE. IgM-producing indicated in reduced data production above significantly the revealed Jointly, 3B). ELISPOT (Figure 3A, Figure in CD27 depicted As qRT-PCR. CD27 tients. findings CD27 above examine The To found. were levels IgM CD27 and CD27 IgG of CD27 IgA, of associations serum deficiency and no numerical levels However, a correlated C4 indicated anti-dsDNA. positively serum were ESR, and levels duration, C3 SLEDAI disease serum levels, and count creatinine platelet serum WBC, 3, Table CD27 and with 2A–L Figures in shown As CD27 of associations The + + + IgD IgD IgD + + + el nSE hc a ofimdb erae g RAlvl seaie yqRT-PCR by examined as levels mRNA IgM decreased by confirmed was which SLE, in cells B + + + IgD IgD IgD el r eoee nSEcsswt ramn-eae ies remission disease treatment-related with cases SLE in recovered are cells B SLE in IgM producing in competent less are cells B + + + elaons eie,CD27 Besides, amounts. cell B + + elaonswr sesdpetetetada ek ottetetinitiation post-treatment weeks 4 at and pre-treatment assessed were amounts cell B el sltdfo cieSEcss(SLEDAI cases SLE active from isolated cells B IgD IgD + + + el’fntoa hne,teraiiyt rdc g a sesdi L pa- SLE in assessed was IgM produce to ability their changes, functional cells’ B + IgD IgD el’ueuns saboakro ies ciiy hte hyaerestored are they whether activity, disease of biomarker a as usefulness cells’ B + + elaonswr soitdwt lnclcaatrsisi L patients, SLE in characteristics clinical with associated were amounts cell B elaonswt eorpi n lnclcaatrsiswr analyzed. were characteristics clinical and demographic with amounts cell B + + IgD + IgD + + IgD IgD IgD + + el ipae eue mut n ucinlimpairment functional and amounts reduced displayed cells B + + + elaon mareti L ainscudb alleviated be could patients SLE in impairment amount cell B elaonswr eakbyeeae Fgr C.Jointly, 4C). (Figure elevated remarkably were amounts cell B elaonsi L ainswr eakbyreduced remarkably were patients SLE in amounts cell B el nSLE. in cells B + + IgD IgD 4 + + el a edl secrete readily can cells B elaonssoe eaiecreain with correlations negative showed amounts cell B + + IgD IgD + + el a mardfnto eadn IgM regarding function impaired had cells B elascae g eecie natural coined were IgM cell-associated B > )adHsudretEIPTand ELISPOT underwent HCs and 5) + IgD + el with cells B Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. .MhjnA eranM uo E laac ecec n elDahPtwy:AMdlfrthe for Model A Pathways: Death Cell and Deficiency 2016;7:35. Clearance Immunol. erythematosus. LE. Front lupus Munoz SLE. systemic M, of of Herrmann Pathogenesis activity A, disease Mahajan for biomarker 6. a as TWEAK 2018;77(1):71-7. 2016;65(6):479-88. Serum Rheumatol. Res. SK. inducer Z Inflamm weak Kim TNF-like nephritis. JY, Urinary lupus Choe RA. of Mohamed 5. biomarker Bax, NN, a Eesa homolog, as M, conserved El-Feqi (TWEAK) El-Fattah a apoptosis Abd with of HA, Taha vivo MN, in Salem 1993;74(4):609-19. heterodimerizes 4. Cell. J Bcl-2 the death. SJ. of cell Korsmeyer review. programmed considerations CL, accelerates comprehensive pathologic Milliman that and A ZN, Clinical Oltvai autoantibodies: A. 3. nephritogenic Doria L, lupus Punzi of 2016;69:1-11. A, aspects Autoimmun. Ghirardello quantitative L, and Iaccarino qualitative M, Immunolog- Gatto immunodeficiency. and 2. erythematosus lupus Systemic 2019:1-9. Y. Yamamoto medicine. D, ical Fujimori T, Sawada manuscript W.; 1. Y. and Y. K.L. H. Z., and F. W. H. L.F., analysis, F. data tools, References , T.W.; analytical revision and and manuscript Z. materials W. Z.; reagents, experiments, W. with K.L.; contribution writing, and H.; W. F. Y. and Z., W. W. design, and conception Study contributions interest. Authors’ of conflict no have authors The Inner Nature the the (81860295), 2019GG052), China Disclosures (201802089, of Project Mongolia(2017MS0809). Foundation Plan Inner Science Technology of Nature Foundation and National Science Science the Region by Autonomous funded Mongolia was study present The investigation. further deserves development SLE in role Acknowledgements precise their although SLE, active detect reliably help revealed research CD27 Overall, previous patients. SLE Our in accumulation repertoire cell BCR factors(25). cells’ apoptotic etiologic reported for potential been CD27 account have as CD27 in diversities also profile disorders, BCR may BCR and/or autoimmune this that TCR and Therefore, Reduced cancer SLE. function. human in CD27 in in patients, development SLE also autoimmunity in but and that quantity, CD27 indicating of in reduced, ability markedly only the was that SLE showed human inflammatory analyses in ELISPOT the and CD27 qRT-PCR that reduced addition, the speculated In explaining we factors the Therefore, investigation. of further one deserves is differentiation(22-24). patients and SLE in activation IFN- environment including cell Cytokines B extent. lead some increasing would to proportions events Since their pathological TNF- patients. of promote SLE imbalance BAFF, and corroborate the in homeostasis characteristics, disordered findings immune functional are altered above different cell-subsets to have The B subsets that cell autoantibodies. indicating B jointly distinct anti-dsDNA 21), and data(20, SLEDAI reported with previously associated negatively and + IgD + el ih lob hne nSE n olwu td sudra osoeCD27 score to underway is study follow-up a and SLE, in changed be also might cells B α, + IgD L6adI-1i h eu fSEptet ffc h elsgaigptwy thereby pathway, signaling cell B the affect patients SLE of serum the in IL-21 and IL-6 + elaonsadfnto r lee nSE hrfr,CD27 Therefore, SLE. in altered are function and amounts cell B + IgD + el sanra nR.Teeoe eseuae htBRpol in profile BCR that speculated we Therefore, RA. in abnormal is cells B 5 + IgD + + IgD IgD + el aedfcsnot defects have cells B + + elaons which amounts, cell B el osceeIgM secrete to cells B + IgD + el could cells B + IgD + γ, B Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. 3 cwihffrE ae ,NsJ atelD clayS mtesN ta.TeBF receptor BAFF The al. et N, Smithers S, 2013;38(3):475-88. McCleary Immunity. pathway. D, signaling receptor Cantrell cell J, B the Nys co-opting L, by Interferon-alpha signals Vanes survival Autoimmun. al. transduces E, J et Schweighoffer Erythematosus. DD, Lupus Gladman 23. Systemic PR, in Fortin function C, and systemic Landolt-Marticorena signaling cell in JJ, 2015;58:100-10. B abnormality Kim transitional permanent TT, altered Li a induces NH, is Chang lymphocytes 2010;12(3):R108. B 22. Ther. IgM Res cells IgD Arthritis frequency of CD27 patients. Decreased population erythematosus blood JA. Brieva lupus new of C, A systemic phenotype Rodriguez in JJ, activated Perez-Venegas al. compartment and A, et memory Ramos-Amaya B, cell J, Rodriguez-Bayona B Brooks 21. the A, 2007;178(10):6624-33. of Pugh-Bernard Immunol. component B, J notable dis- Zheng a erythematosus. to represents A, lupus autoantibodies CD27 Cappione of IgM J, expression Anolik GJ. lacking C, Silverman in Wei M, disease chronic renal 20. Petri 2012;142(3):390-8. and and RW, Immunol. events Autoimmunity cardiovascular Burlingame Clin from SLE. C, protection with al. Oh with patients et correlate E, antigens G, Akhter apoptosis-associated Schett tinct C, 2010;10(1):38- K, Gronwall Rev. Sarter Autoimmun 19. SLE. C, of Schorn etiopathogenesis the C, in Schulze steps 42. C, clearance-related IgM-dependent two Janko - of LE, inflammation role Munoz Predominant M. macrophages 2005;35(1):252-60. marrow-derived 18. Botto bone Immunol. murine MJ, by J cells Walport Eur dying of MR, vitro. clearance the in pathogenesis Ehrenstein in the pathway PK, classical in the Potter Apoptosis of activation J. P, dead Vlag Quartier of der van role M, 2008;17(5):371-5. 17. Herrmann The Lupus. J, Berden erythematosus. al. S, lupus potential Franz et systemic as C, Bavel of M, cells van dendritic Herrmann LE, Munoz erythematosus: C, 2014;10(9):1151-64. lupus 16. Berens systemic Immunol. R, of Clin Chaurio pathogenesis Rev and Expert C, etiology targets. Maueroder the S, in Veissi clearance cell MH, nephritis. Biermann lupus J and erythematosus 15. lupus 2000. systemic of index pathogenesis activity the 2017;185:59-73. in disease Immunol. death Cell Clin erythematosus MJ. Kaplan lupus P, Mistry Systemic 14. MB. Urowitz D, 2002;29(2):288-91. of Ibanez classification Rheumatol. DD, the Gladman for Gene criteria Altered 1997;40(9):1725. revised 13. With Rheumatology Rheum. Cells of B Arthritis College CD27(+)IgD(+) erythematosus. Impaired American lupus the al. systemic Updating et MC. L, Hochberg Xu 2018;9:626. Y, 12. Immunol. Jia Front X, 2013;10(2):113-21. Liu Arthritis. Immunol. L, Rheumatoid Mol Shi in Cell W, Signature Zhang cells. F, B Hu innate-like repertoire. 11. of immunoglobulin ”memory” functions prediversified IgM Regulatory a X. blood harboring Human Zhang cells al. 10. B et ME, zone Conley marginal C, 2004;104(12):3647-54. splenic Cordier Blood. A, circulating Rosenwald are 1999;96(5):2250-5. of BK, acquired cells Tan America. Proceedings MC, and B of system. Braun Innate States immune S, United LA. Weller the the of Herzenberg 9. of arms LA, Sciences distinct Herzenberg by of L, Academy mediated Brown are National GC, virus the influenza Jager to OC, immunities Herman humoral Diseases. N, Autoimmune Baumgarth Cell-Mediated B 8. of Development the 2016;36(2):163-77. and Immunol. IgM Natural Rev N. Crit Baumgarth TT, Nguyen 7. 6 Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. oe aaaemean are Data Note: remission cell experiencing of blood patients features White SLE WBC, clinicodemographic Index; post-treatment Activity and Disease Pre- SLE 2 Table SLEDAI, erythematosus; lupus systemic SLE, Note: 2016;166(6):1362-4. Cell. features patient Cancer. dysregulated SLE in Dysfunction 1 and Table Cell cytokines T of key Diversity the amongst Probing connections SM. Kaech Developing RT, 2012;24(6):658-64. Sowell CG. Immunol. 25. Vinuesa Opin Curr SK, autoimmunity. Lee in centers RA, germinal Sweet 24. g,yas50 (N=12) treatment After (N=12) treatment Before years Age, Characteristic eaeml 0210/2 0.72 8 10/2 177.8 g/L C3, Serum IU/mL Anti-dsDNA, score SLEDAI Female/male eu 4 / 0.09 g/L C4, Serum B,10 WBC, eu Creatinine, Serum 10 Platelet, rnr rtis /4 1.73 g/24h proteins, Urinary ± 9 D *p SD. L2.98 /L rnr rtis /4,ma(ag)0.4(0-3.4) 0.19(0.03-0.40) 14.35(7.4-29.2) 0.94(0.26-1.51) 46/4 mean(range) g/24h, proteins, Urinary (mean 1012/L (N=50) Platelet, SLE (mean 3.8(0-12) 109/L WBC, Creatinine, 244.5(100-659) Serum 45.6(17-67) mean(range) g/L, C4, Serum mean(range) g/L, C3, Serum mean(range) g/L, IgG, mean(range) IU/mL, 6.8(1-30) Anti-dsDNA, mean(range) score, years SLEDAI mean(range), diagnosis, of Duration Female/male years mean(range), Age, Characteristic 12 L124.0 /L < .5 **p 0.05, μ o/ 102.58 mol/L < μ ± .1 ***p 0.01, o/,ma(ag)87.99(56-189) mean(range) mol/L, ± ± 2 2 250 12 ± ± ± ± D 3.75 SD) ± ± .41.25 0.34 .70.21 0.07 .73.53 1.57 .80.20 1.58 ± ± 13 98.92 51.32 59157.08 65.9 11 87.83 31.16 D 171.76 SD) 7 < .0 s r-ramn values pre-treatment vs. 0.001 ± ± ± 2*** 12 ± ± ± ± 1.04 ± ± ± 0.46* 0.10* 0.63 0.19** ± 70.76 28.55** 20.39 69.94 Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. o infiat **p significant. not patients. mean CD27 (n=50) are of HC Percentages Data and (C) patients. (n=50) panel) SLE (right in SLE and cells panel) B (left HC representative from na¨ıveobtained (CD27 identifying for (CD27 strategy memory Gating (A) patients. (HC) CD27 Circulatory 1. Fig. ± + Do einaditrurierne aapit ersn niiulpriiat.NS, participants. individual represent points Data range. interquartile and median or SD IgD < - .1 ***p 0.01, n obengtv (CD27 negative double and ) + IgD + < elaonsaerdcdi L ae ncmaio ihhatycontrol healthy with comparison in cases SLE in reduced are amounts cell B 0.001 - IgD 8 - el nhmnbod B CD27 (B) blood. human in cells B ) - IgD + ,int-ie(CD27 innate-like ), + IgD + + IgD ,switched ), + cells B + IgD + Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. odfn niae aigsaitclsgicne *P significance. statistical having indicates font Bold applied was test Spearman SLE The in features (L). patient IgM with amounts and cell (K) B CD27+IgD+ IgG of (J), Associations disease IgA 3 (F), Table Anti-dsDNA (I), (E), C4 SLEDAI (D), serum Creatinine (H), Serum (*P (C), ESR C3 (G), serum (B), duration count Platelet (A), count CD27 of Associations Fig.2 < .5 **P 0.05, < 0.01). + IgD + g 0250.101 0.218 -0.235 0.348 0.100 0.177 -0.136 0.235 0.051 -0.278 0.125 -0.022 IgG IgM IgA C4 ESR Duration ds-DNA SLEDAI Creatinine Serum C3 PLT WBC manifestation clinical elaonswt L ain ies aiettos nldn WBC including manifestations, disease patient SLE with amounts cell B 9 < .5 **P 0.05, 0470.000** 0.000** -0.477 0.045* -0.724 0.003* 0.285 0.004* 0.415 P 0.017* 0.396 0.337 r < 0.01. Posted on Authorea 28 Oct 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.160387924.49172232/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. eoeadatrtetet(=2.(*P (n=12). CD27 (C) treatment after (n=12). patients and SLE before in treatment after and before scores CD27 CD27 of assessment 4. Fig. are quantitation and charts Representative detection. 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