Faculty Bibliography

Background SLE is an archetypical systemic autoimmune disease,which has been attributed to interactions between genetic andenvironmental factors that are currently not well understood. Yetrecent reports have begun to elucidate how intestinal bacteriainfluence the development of physiologic B-cell/T-cell responses,and can affect the pathogenesis of inflammatory and autoimmuneconditions. Our studies are designed to shed light on the potential roles of the gut microbiome in SLE pathogenesis.Methods We have assembled and characterised a cohort of 60female SLE patients and 20 healthy controls. DNA from theunfractionated bacteria in faecal samples, and from the sortedendogenous IgA-coated and non-coated bacterial fractions, wasthen extracted. 16 S bacterial rRNA genes were then barcodedand amplified, and over 20,000 reads were determined per sample using illumina NGS technology. Faecal and serum total Ig andautoantibodies were measured by ELISA.Results Our analysis showed less microbiome diversity in SLEthan healthy controls (p = 0.002). This dysbiosis was treatmentindependent, with more severe intestinal dysbiosis and decreasedbacterial diversity in patients with high disease activity, based onSLEDAI. In addition, SLE patients had increased representationof certain bacterial families, genus's and species, based on 16 SrRNA assignments of operational taxonomic units (OTUs).Patients with active disease displayed contractions of bacterialtaxa with reported protective properties and reciprocal expansions of taxa with putative pathobiont properties. We alsoassessed IgA, which is the most prevalent antibody isotype madeby the human body, and found evidence of exuberant levels inboth intestinal and blood samples of SLE patients. While only aminority of bacterial taxa are specifically coated by endogenousintestinal IgA, IgA-coated bacteria in SLE patients had differentialrepresentation with recurrent taxa-specific expansion in SLEpatients. Strikingly, Prevotella copri, which has recently beenlinked to new-onset RA, was significantly over-representedamong the IgA-coated taxa only in SLE patients with high diseaseactivity, and was not detected in healthy controls.Conclusion Our studies provide the first evidence that SLE isassociated with gut microbiome dysbiosis with expansions of specific bacterial taxa that may contribute to immune dysregulation.This imbalance was more significant in patients with high diseaseactivity Characterisation of in vivo IgA-coated bacteria demonstrated that certain microbes taxa/species are preferentially recognised by the adaptive immune system of SLE patients, and thesediffer significantly from healthy adults. We are now studyingthese candidate pathobionts in longitudinal studies to addresswhether the microbiome predicts and/or tracks flares

Background Progress in the management of pregnancy in patientswith lupus and asymptomatic women with anti-Ro antibodies hasbeen made on several fronts in the last year.Results Data from the PROMISSE study (Predictors of PRegnancy Outcome: Bio Markers In Antiphospholipid Syndrome andSystemic Lupus Erythematosus) under the leadership of Dr. JaneSalmon which enrolled 389 women with or without anti-phospholipid antibodies, identified several important and potentiallyactionable baseline predictors of adverse pregnancy outcomes(APO). These include: taking hypertensive medications, having aplatelet count less than 100 k, being positive for the lupus anticoagulant (LAC), and having a physician global assessment of lupusactivity at >1. The absence of a rise in C3 during the second trimester also constituted a risk factor. Being non-Hispanic whitewas protective. Both mild/moderate and severe flares were infrequent, 13% and 3%, respectively. De novo renal disease was rare,occurring in 3/265 patients who never met ACR renal criteria.Overall, in patients with no risk factors at baseline, the APO ratewas 7.8%; fetal/neonatal mortality 3.9%. In contrast, in patientswho are either LAC positive, or LAC negative but non-White andtreated with antihypertensives, the APO rate was 58%; fetal/neonatal mortality 22%. With regard to clinical and basic translational work in neonatal lupus, there have been several advances.Based on review of 156 cases of heart block absent any extranodal involvement the use of fluorinated steroids did not reversethe block, influence the cumulative probability of extranodal disease, the cumulative probability of survival, or the cumulativeprobability of pacemaker implantation. Accordingly, these datado not support the use of dexamethasone in isolated block forthe sole purpose of preventing more progressive disease. Evaluation of umbilical cord blood from 139 anti-Ro exposed neonateswith and without heart block suggests innate and parenchymalimmune cell activation in the affected fetus. Specifically, cordCRP, NT-proBNP, MMP-2, uPA, uPAR, and plasminogen levelswere higher in affected fetuses than in unaffected cases, independent of maternal rheumatic disease, season at highest risk ofheart block, and medications taken during pregnancy. These biomarkers were positively associated with a disease severity scorederived from known risk factors for mortality. Based on the consistent demonstration of fibrosis of the atrioventricular node surrounded by macrophages and multinucleated giant cells in antiRo antibody exposed fetuses dying with heart block, investigational studies focused on macrophage signalling stimulated byssRNA associated (hY3) with the Ro60 protein and the impact ofantagonising innate cell drivers such as TLR7/8. Ligation ofTLR7/8 resulted in increased histone methylation as measured byincreased H3K4me2, a requirement for binding of NF-kB at certain promoters, specifically the kB1 region in the TNF promoterwhich was significantly decreased by hydroxychloroquine.Conclusion Translation of these finding to the bedside suggeststhat hydroxychloroquine may be efficacious in preventing heartblock. An ongoing study is currently addressing secondaryprevention

Background When found in the absence of antibodies toextractable nuclear antigens (ENA) or anti-double-stranded DNA(dsDNA) (i.e., monospecific), autoantibodies to the nuclear autoantigen dense fine speckles 70 (DFS70) are purported to ruleout SLE. The reported frequency of anti-DFS70 by chemiluminescence (CIA) in SLE is low compared to healthy individuals(0-5.7% vs. 1.3-23.2%), while the frequency of monospecificanti-DFS70 in SLE is even lower at 0-0.4%. There are no studies examining the frequency of anti-DFS70 in an early inceptionSLE cohort. This study determined the prevalence of antiDFS70 in a multi-national, multi-ethnic early inception SLEcohort and examined demographic, clinical, and autoantibodyassociations.Materials and methods Patients fulfilling ACR Classification Criteria for SLE were enrolled in the Systemic Lupus InternationalCollaborating Clinics (SLICC) inception cohort within 15months of diagnosis. Demographic and clinical data were collected at enrollment. ANAs were detected by indirect immunofluorescence on HEp-2 cells (ImmunoConcepts, Sacramento)and ENAs and dsDNA by an addressable laser bead immunoassay (FIDIS Connective13, TheraDiag, Paris). Anti-DFS70 antibodies were measured by CIA (Inova Diagnostics, San Diego).The association between anti-DFS70 and baseline demographic,clinical, and autoantibody profiles was assessed using univariateand multivariate logistic regression. For the most informativemodel, only the remaining statistically significant predictors atthe 95% CI: were included, after eliminating other potentialpredictors individually, starting with the least likely to be associated with the outcome.Results 1137 patients were included; 89.9% were female and93.8% were ANA positive (Table 1). The frequency of antiDFS70 was 7.1% [95% CI: 5.7-8.8%]. 13 of 1137 (1.1%)[95% CI: 0.6-1.9%] were positive for anti-DFS70 only (monospecific). In univariate analysis, patients with musculoskeletalactivity (based on SLEDAI items) or anti-b-2 glycoprotein-1(anti-b2GP1) were more likely to have anti-DFS70, whereasthose with anti-dsDNA, anti-SSA/Ro60, anti-SSB/La, or antiU1RNP were less likely to have anti-DFS70. In multivariateanalysis, patients with musculoskeletal activity (Odd Ratio (OR)1.25 [95% CI: 1.10, 1.41]) or anti-b2GP1 (OR 2.15, 95% CI:1.21, 3.84) were more likely to have anti-DFS70, while thosewith anti-dsDNA (OR 0.53, 95% CI: 0.31, 0.92) or anti-SSB/La(OR 0.25, 95% CI:0.08, 0.82) were less likely to have antiDFS70.Conclusions The prevalence of anti-DFS70 in newly diagnosedSLE patients was at the high end of the range previouslypublished for SLE (7.1% vs. 0-5.7%) and was associated withmusculoskeletal activity and anti-b2GP1. However, 'monospecific' anti-DFS70 was rare (1.1%) and is potentially useful to discriminate between ANA positive healthy individuals and SLE

Background/Objective: Thrombocytopenia is a common feature of both SLE and antiphospholipid syndrome (APS) and in former most frequently results from antiplatelet antibodies (ie AITP) or antiphospholipid antibodies (aPL). Patients with AITP paradoxically have an increased risk of thrombosis and it has been speculated that this can result from co-presence of aPL. Primary APS is associated with both thrombosis and thrombocytopenia. We assessed whether there was an association between a history of thrombocytopenia and prevalence of a thrombotic event in a large, multiethnic cohort of SLE patients. Methods: We analyzed the NYU SLE SAMPLE Registry, consisting of patients fulfilling ACR and/or SLICC criteria for SLE. We identified 105 patients whose SLE criteria included the presence of one or more of the following APLS antibodies: lupus anticoagulant; IgG or IgM anti-beta2-glycoprotein-I; IgG or IgM anticardiolipin antibodies, and determined whether these patients had thrombocytopenia among their SLE classification criteria (<100,000/muL). We reviewed each patient's medical record to identify the prevalence of thrombosis (defined as DVT, PE, CVA, arterial occlusion with gangrene or amputation), and/or obstetric events. We compared the prevalence of thrombotic events in SLE patients with and without history of thrombocytopenia. Results The NYU SLE SAMPLE currently includes 612 patients (90% female, mean age 43.0+/-0.9 years, and 10% men, mean age 41.0+/-0.3 years). 54% of subjects were white, 31% African American, and 15% Asian. 30% were Hispanic White, and 5% Hispanic Black. 17% had aPL, of whom 89% were female and 11% male (mean age 43.0+/-0.2 years, 56% Caucasian, 33% African American, and 11% Asian). 24% were Hispanic white and 4% Hispanic Black. The total numbers of patients with thrombotic events were 45 (43%), with 5/21 (23%) in the SLE patients with aPL and prior history of thrombocytopenia and 40/ 84 (47%) (p=0.042) in the patients without thrombocytopenia. The most common thrombotic event was DVT followed by CVA. Conclusion The prevalence of aPL in the NYU SLE registry was 17%, and adverse thrombotic events were less common in the patients with prior history of thrombocytopenia (5/21, 23%) as compared to those without (40/84, 47%). This unexpected finding could be explained by protective benefit of antiplatelet antibodies when co-occur with aPL in SLE or less thrombogenic aPL in SLE when produces thrombocytopenia. Additionally, our data suggest that there might be different consequences of aPL between primary APS patients and SLE patients with aPL

Background/Objective: We and others have suggested that complement activation can serve as an initiating signal that increases the thrombosis risk in SLE patients with antiphospholipid antibodies (aPL). Generation of complement activation products can result in proinflammatory and/or prothrombotic responses providing a permissive environment for the pathological effects of antibodies to negatively charged phospholipid protein complexes. Methods: We analyzed the NYU SLE SAMPLE Biorepository initiated in September 2013, which consists of 599 patients fulfilling ACR and/or SLICC criteria for systemic lupus erythematosus. We identified 98 patients whose criteria included the presence of one or more for the following aPL: lupus anticoagulant, IgG or IgM anti-beta2- glycoprotein-I, or IgG or IgM anticardiolipin antibodies and determined if these patients received SLEDAI points for hypocomplementemia during any encounter. We then reviewed each patient's medical record to identify the prevalence of thrombosis defined as DVT, PE, CVA, arterial occlusion with gangrene or amputation, and obstetric events as well as noncriteria manifestation of thrombocytopenia or valvulitis. We then compared the prevalence of these APLS manifestations in the SLE patients with and without evidence of complement activation. Results: The NYU SLE SAMPLE biorepository includes 599 patients (90% female, mean age 43.0+/-.9, and 10 % men, mean age 41.0+/-.3, 54% Caucasian, 31% African American, 15% Asian, 30% Hispanic White, and 5% Hispanic Black). 98 of the 599 SLE patients had aPL, 86 female and 12 male (mean age 43.0+/-.2, 56% Caucasian, 33% African American, and 11% Asian). 24 % were Hispanic white and 4% Hispanic Black. The total number of patients with adverse events was 54 of 98 (55%) with 33/50 (66%) in the SLE patients with aPL and evidence of hypocomplementemia and 21/48 (43%) (p=0.04) in the patients without evidence of hypocomplementemia. The most common thrombotic event was DVT followed by CVA. Conclusions: The prevalence of aPL as a criteria in the NYU SLE registry is 98 of 599, and adverse events were more common in the patients with evidence of hypocomplementemia (33/50, 66%) as compared to the patients without complement activation (21/48, 43%). These findings can inform decisions regarding which patient subsets that may benefit from the prophylactic use of low-dose aspirin for primary prevention in asymptomatic lupus patients. Moreover, future clinical trials should be stratified on the basis of complement consumption to be sure that equal numbers of these patients appear in both the experimental and comparator treatment arms. Finally, future prospective studies should explore the interaction between complement activation products, platelets, neutrophils, mononuclear cells, endothelial cells, coagulation cascade in the adverse events that constitute antiphospholipid syndrome

Background/Objective: Few studies have analyzed the risk factors for thrombosis in SLE patients with antiphospholipid antibodies and most had small sample sizes and homogenous patient populations. We examined whether a history of nephritis is a risk factor for thrombosis using a large multi-ethnic SLE cohort. Methods: The NYU SLE SAMPLE Biorepository and Registry was initiated in September 2013 and includes 612 patients fulfilling ACR and/or SLICC criteria for SLE. Within SAMPLE, we identified patients with a positive test for antiphospholipid antibodies (aPL) (lupus anticoagulant, IgG or IgM anti-beta2-glycoprotein-I antibodies, IgG or IgM anticardiolipin antibodies) and determined if these patients had also ever fulfilled nephritis criteria. We reviewed each patient's medical record for presence/absence of thrombosis (DVT, PE, CVA, arterial occlusion with gangrene or amputation), and obstetric events as well as the noncriteria manifestations thrombocytopenia or valvulitis. We compared the prevalence of APLS manifestations in SLE patients with and without history of lupus nephritis. Results: Of the initial 612 SLE patients, 90% were female (mean age 43.0+/-0.9 years), and 10% were male (mean age 41.0+/-0.3 years). 54% were white, 31% African American, and 15% Asian; 30% were Hispanic white, and 5% Hispanic Black. 105 of the 612 patients had aPL, including 93 females and 12 males (mean age 43.0+/-0.2 years, 56% Caucasian, 33% African American, and 11% Asian). 24% were Hispanic white and 4% Hispanic Black. The total number of patients with thrombotic events was 45/105 (43%), including 26/43 (60%) in the nephritis subset and 19/62 (30%) (p: 0.04) among patients without prior renal involvement. The most common thrombotic event was DVT followed by CVA. Conclusion: The prevalence of aPL criteria in NYU SLE SAMPLE was 17%. Within this group, adverse events were more common among the patients with, versus without, prior history of renal involvement (60% vs 30%). It remains uncertain if association is explained by different accompanying antibodies that distinguish nephritis from non-nephritis SLE, e.g., dsDNA, complement, or drug treatment. This observation provides further support for universal use of hydroxychloroquine in SLE especially in setting of nephritis and suggests that event-free aPL positive patients with prior history of nephritis may be at increased risk for future thrombosis. Further studies are needed to determine whether such patients could benefit from prophylaxis with aspirin or other mild antithrombotic agents

Background/Purpose: Few studies have analyzed the risk factors for thrombosis in Systemic Lupus Erythematosus (SLE) patients with antiphospholipid antibodies (aPL) and most had small sample sizes and homogenous patient populations. We examined whether a history of nephritis is an additional risk factor for thrombosis on a large multi-ethnic SLE cohort database. Methods: The NYU SLE SAMPLE biorepository and registry was initiated in September 2013 and includes 612 patients fulfilling ACR and/or SLICC criteria for SLE. Within SAMPLE, we identified patients with a positive aPL test (lupus anticoagulant, IgG or IgM anti-beta2- glycoprotein-I antibodies and/or IgG or IgM anticardiolipin antibodies) and determined if these patients had also ever fulfilled nephritis criteria. We reviewed each patient's medical record for presence/absence of venous and arterial thrombosis, and obstetric events as well as the non-criteria manifestations such as thrombocytopenia or valvulitis. We compared the prevalence of antiphospholipid syndrome (APS) manifestations in SLE patients with and without a history of lupus nephritis. Results: Of the initial 612 SLE patients (90% female; mean age 43.0+/-0.9 years), 54% were Caucasian, 31% African American, 15% Asian; 30% Hispanic white, and 5% Hispanic Black. Of the 612 patients, 105 had aPL, including 93 females and 12 males (mean age 43.0+/-0.2 years), 56% Caucasian, 33% African American, 11% Asian, 24% Hispanic white and 4% Hispanic Black. The total number of patients with thrombotic events was 45/105 (43%), including 26/43 (60%) in the nephritis subset and 19/62 (30%) (p=0.04) among patients without prior renal involvement. The most common thrombotic event was deep vein thrombosis (DVT) followed by stroke. Conclusion: The prevalence of APS criteria in the NYU SLE SAMPLE was 17%. Within this group, adverse events were more common among the patients with, versus without, a prior history of renal involvement (60% vs 30%). It remains uncertain if this association can be explained by, for example, by the presence of other accompanying findings that distinguish nephritis from non-nephritis SLE (e.g. anti-dsDNA, complement consumption) or drug treatment. This observation provides further support for the universal use of hydroxychloroquine in SLE, especially in those with current or previous nephritis and suggests that event-free aPL positive patients with a prior history of nephritis may be at increased risk for future thrombosis. Further studies are needed to determine whether such patients could benefit from prophylaxis with low-dose aspirin, statins or even other mild anti-thrombotic agents

Background/Purpose: Previous studies have established the value of measuring complement activation products (C4d) bound to platelets (PC4d) for the diagnosis and monitoring of Systemic Lupus Erythematosus (SLE). Separately, Antiphospholipid (APL) antibodies have been associated with complement activation and PC4d expression. In this study, we sought to validate the performance characteristics of PC4d, stratified by the presence or absence of APL antibodies. Methods: This multi-centered validation cross sectional study (16 sites in the US) enrolled 402 SLE subjects fulfilling the 1982 American College of Rheumatology Criteria revised in 1997 (mean age 41 years; 91% female), 411 subjects with rheumatic and autoimmune diseases other than SLE (mean age 55, 86% female consisting of 181 rheumatoid arthritis, 90 primary fibromyalgia, 92 other rheumatic diseases, and 48 autoimmune thyroiditis or hepatitis) and 198 healthy volunteers (mean age 41 years; 66% female). PC4d densities were determined using flow cytometry (expressed as mean fluorescence intensity [MFI]). Positive PC4d consisted of PC4d levels greater than 20 net MFI. Anticardiolipin IgG, anti-Beta-2-glycoprotein 1 IgG, or anti-Phosphatidylserine/Prothrombin (PSPT) complex IgG antibodies were determined using ELISA (INOVA diagnostics, San Diego, CA). Presence of APL antibodies consisted of any of these antibodies above manufacturer cutoff. SLE Disease activity was assessed using the non-serological SLE Disease Activity Index SELENA modification (ns-SELENA-SLEDAI, without the complement and anti-dsDNA). Performance characteristics were established using sensitivity, specificity, and ROC Curve Area Under the Curve (AUC). Statistical evaluation was by t-test (for disease activity), by chi-squared test for equality of proportions (for sensitivities and specificities) and by the method of DeLong (for ROC Curve AUC). Results: PC4d was highly specific in distinguishing SLE from other rheumatic diseases (Table) and normals. Among SLE subjects, 47% (n=187) presented with at least one APL antibody as compared to 21% (n=86) of subjects with other diseases and 15% of normals. PC4d sensitivity for SLE was higher among APL positive subjects by comparison to APL negative subjects (p=0.003). Specificity was not significantly different between APL positive and negative subjects (p>0.372). ROC AUC was significantly higher among the APL positive compared to negative subjects (p=0.002). The incidence of APL antibodies among all PC4d positive subjects was 60% compared to 27% among PC4d negative subjects (p<0.001). SLE subjects presenting with positive PC4d had higher disease activity (4.1+/-0.5) than those presenting with negative PC4d (3.0+/-0.2) (p=0.03). Conclusion: We confirm that PC4d is highly specific for SLE, and is associated with disease activity. (Table Presented)

Background/Purpose: Thrombocytopenia is a common feature of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and in the former most frequently results from antiplatelet antibodies (i.e., AITP) or aPL antibodies. Patients with AITP paradoxically have an increased risk of thrombosis and it has been speculated that this can result from co-presence of aPL. Primary APS is associated with both thrombosis and thrombocytopenia. We assessed whether there was an association between a history of thrombocytopenia and the prevalence of a thrombotic event in a large, multiethnic cohort of SLE patients. Methods: We analyzed the NYU SLE SAMPLE registry, consisting of patients fulfilling ACR and/or SLICC criteria for SLE. We identified 105 patients whose SLE criteria included the presence of one or more of the following aPL antibodies: lupus anticoagulant, IgG or IgM anti-beta2-glycoprotein-I, and/or IgG or IgM anticardiolipin antibodies; and determined whether these patients had thrombocytopenia (<100,000/muL) recorded among their SLE classification criteria. We reviewed each patient's medical record to identify the prevalence of arterial or venous thrombosis (defined as DVT, PE, stroke, arterial occlusion with gangrene or amputation), and/or obstetric events. We compared the prevalence of thrombotic events in SLE patients with and without history of thrombocytopenia. Results: The NYU SLE SAMPLE currently includes 612 patients (90% female, mean age 43.0+/-0.9 years, and mean age of 41.0+/-0.3 years in the males); 54% of the subjects were Caucasian, 31% African American, 15% Asian, 30% Hispanic White, and 5% Hispanic Black: 17% had aPL antibodies, of whom 89% were female and 11% male (mean age 43.0+/-0.2 years, 56% Caucasian, 33% African American, and 11% Asian, 24% Hispanic white and 4% Hispanic Black). The total numbers of patients with thrombotic events were 45 (43%), with 5/21 (23%) in the SLE patients with aPL and prior history of thrombocytopenia and 40/84 (47%; p=0.042) in the patients without thrombocytopenia. The most common thrombotic event was DVT followed by stroke. Conclusion: The prevalence of aPL in the NYU SLE registry was 17%, and adverse thrombotic events were less common in the patients with prior history of thrombocytopenia (5/21, 23%) as compared to those without (40/84, 47%). This unexpected finding could be explained by protective benefit of anti-platelet antibodies when co-occur with aPL in SLE, or less thrombogenic aPL in SLE when there is concomitant thrombocytopenia. Additionally, our data suggest that there might be different consequences of aPL between primary APS patients and SLE patients with aPL

Background/Purpose: SLE is a complex multifactorial systemic autoimmune disease, which has been attributed to poorly understood interactions between genetic and environmental factors. Recent reports have begun to elucidate how imbalances within intestinal communities of commensal bacteria may lead to triggering of inflammatory and autoimmune conditions. Our studies are designed to shed light on the interactions of the immune system and the gut microbiome that may contribute to lupus pathogenesis. Methods: We have assembled a cohort of 60 female SLE patients and matched 20 healthy controls, and biobanked blood and stool samples. DNA was then extracted from fecal bacterial samples, and from sorted endogenous IgA-coated and non-coated bacterial fractions. 16S bacterial rRNA gene sequencing was then performed by illumina NGS technology. Fecal and serum total Igs and autoantibodies were measured by ELISA and by multiplex-bead autoantigen assays. Results: Our analyses showed that SLE patients have significantly reduced diversity (i.e., number of different taxa) in their gut microbiomes compared to controls (p=0.038). This dysbiosis was treatment independent, with more marked contractions in patients with high disease activity, based on SLEDAI (p=0.002). The distribution of microbiome taxa was more heterogeneous among SLE patients than healthy individuals (p=0.002). Interestingly, patients with the most active disease commonly displayed expansions of genus and species with putative pathobiont properties, with reciprocal contractions of others associated with protective properties (e.g. R. gnavus (p= 0.001) vs. F. prausnitzii (p= 0.022) and B. uniformis (p=0.016). In immunologic surveys, we found that IgA (the most highly produced Ig isotype in the body), was significantly elevated in SLE patients compared to healthy subjects (p<0.002). Only a limited proportion of bacterial taxa are specifically coated by endogenous intestinal IgA. Yet, SLE patients with high disease activity displayed an increased abundance among IgA-coated taxa of Prevotella copri (p= 0.018), a species which has recently been linked to new-onset RA. In addition, intestinal IgA in SLE patients included high levels of antibodies to lupus autoantigens, with the same IgA autoantibody profiles in the matched sera of individual patients. Conclusion: Our studies document that SLE is associated with a dysbiosis in the gut microbiome with expansions of specific pathobiont bacteria and reciprocal contractions that may contribute to immune dysregulation. This imbalance was more significant in patients with high disease activity. Certain microbial taxa/species are preferentially recognized by the adaptive immune system of SLE patients and coated in vivo by intestinal IgA, and this correlated with elevated overall levels of fecal and serum IgA. Taken together, these data support the hypothesis that the pathogenesis of SLE may arise from imbalances in the gut microbiome and immune recognition of certain bacterial taxa