IgG, IgM, and IgA Antinuclear Antibodies in Discoid and Systemic Lupus Erythematosus Patients

Jost, Sheridan A.; Tseng, Lin Chiang; Matthews, Loderick A.; Vasquez, Rebecca; Zhang, Song; Yancey, Kim B.; Chong, Benjamin F.

doi:10.1155/2014/171028

Cited by 29 publications

(23 citation statements)

References 23 publications

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“…B. theta monocolonization plus IMQ led to increased levels of anti- hRo60 compared to all other conditions but did not enhance other lupus autoantibody titers, likely due to the short study period of 8 weeks that does not yet allow for epitope spreading, which takes years in humans (1, 44). Despite this, lupus nephritis–like immune complex deposition composed of C1q, C3, IgG, IgA, and IgM (45–47) was detectable in 88% of all glomeruli of the IMQ-treated B. theta –monocolonized mice (37 of 42 glomeruli) compared to only 4 of 49 glomeruli involved in IMQ-treated GF mice (Fig. 8L shows representative images of immunofluorescence), indicating a systemic autoimmune effect.…”

Section: Resultsmentioning

confidence: 98%

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

et al. 2018

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The earliest autoantibodies in lupus are directed against the RNA binding autoantigen Ro60, but the triggers against this evolutionarily conserved antigen remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and gut commensal bacterial species and confirmed the presence of these orthologs in patients with lupus and healthy controls. Thus, we hypothesized that commensal Ro60 orthologs may trigger autoimmunity via cross- reactivity in genetically susceptible individuals. Sera from human anti-Ro60–positive lupus patients immunoprecipi-tated commensal Ro60 ribonucleoproteins. Human Ro60 autoantigen–specific CD4 memory T cell clones from lupus patients were activated by skin and mucosal Ro60-containing bacteria, supporting T cell cross-reactivity in humans. Further, germ-free mice spontaneously initiated anti-human Ro60 T and B cell responses and developed glomerular immune complex deposits after monocolonization with a Ro60 ortholog–containing gut commensal, linking anti- Ro60 commensal responses in vivo with the production of human Ro60 autoantibodies and signs of autoimmunity. Together, these data support that colonization with autoantigen ortholog-producing commensal species may initiate and sustain chronic autoimmunity in genetically predisposed individuals. The concept of commensal ortholog cross-reactivity may apply more broadly to autoimmune diseases and lead to novel treatment approaches aimed at defined commensal species.

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Section: Resultsmentioning

confidence: 98%

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

et al. 2018

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“…54 Indeed, some studies suggest that IgM anti-DNA antibodies may be protective, 55 whereas other isotypes may also play a role in disease. [56][57][58] However, there are no systematic BCR sequencing studies in SLE that incorporate analysis of isotypes. Isotype-resolved BCR repertoire sequencing on peripheral blood or tissue Bcells subpopulations may be able to provide clues to the extent to which a particular clone has undergone CSR and the relative contributions of each isotype to a certain autoantibody specificity.…”

Section: Isotype In Slementioning

confidence: 99%

Antibody repertoire analysis in polygenic autoimmune diseases

2018

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SummaryHigh‐throughput sequencing of the DNA/RNA encoding antibody heavy‐ and light‐chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B‐cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B‐cell development at which this occurs. The advent of technologies, such as whole‐genome sequencing, offers the chance to link abnormalities in the B‐cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B‐cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B‐cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B‐cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear.

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“…On the other hand, serum IgA levels, but not IgG or IgM levels, were diminished in lupus-prone mice that received oral treatment with Lactobacillus, which suppresses lupus nephrites 23 . Importantly, anti-DNA antibodies of IgA class are found in the serum of patients with SLE [24][25][26][27][28][29] , suggesting that they may be of gut primed B cell origin. These reports along with our studies 16,17 showing pro-inflammatory immune phenotype and higher plasma cell frequency by lupusprone female mouse intestine suggests the degree of IgA secretion in the gut lumen could show gender bias and may be indicative of lupus susceptibility and autoimmune progression.…”

Section: Introductionmentioning

confidence: 99%

Abundance and nuclear antigen reactivity of intestinal and fecal Immunoglobulin A in lupus-prone mice at younger ages correlate with the onset of eventual systemic autoimmunity

Sun

Gudi

Johnson

et al. 2020

Preprint

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Our recent studies, using (SWRxNZB)F1 (SNF1) mice, showed a potential contribution of the gut microbiota and pro-inflammatory immune responses of the gut mucosa to systemic autoimmunity in lupus. Here, using this mouse model, we determined the abundance and the nAg reactivity of IgA antibody produced in the intestine under lupus susceptibility. Intestinal lymphoid tissues from SNF1 mice, females particularly, showed significantly higher frequencies of nAg (dsDNA and nucleohistone) reactive IgA producing B cells compared to B6 females. Most importantly, younger age fecal IgA -abundance and - nAg reactivity of lupus-prone mice showed a positive correlation with eventual systemic autoimmunity and proteinuria onset. Depletion of gut microbiota in SNF1 mice resulted in the diminished production of IgA in the intestine and the nAg reactivity of these antibodies. Overall, these observations show that fecal IgA features, nuclear antigen reactivity particularly, at preclinical stages/in at-risk subjects could be predictive of autoimmune progression.

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IgG, IgM, and IgA Antinuclear Antibodies in Discoid and Systemic Lupus Erythematosus Patients

Cited by 29 publications

References 23 publications

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

Antibody repertoire analysis in polygenic autoimmune diseases

Abundance and nuclear antigen reactivity of intestinal and fecal Immunoglobulin A in lupus-prone mice at younger ages correlate with the onset of eventual systemic autoimmunity

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