Rheumatoid Factor Reactivity of Expanded <scp>CD</scp>21<sup>−/low</sup> B Cells in Patients With Sjögren's Syndrome: Comment on the Article by Glauzy et al

Bende, Richard J.; Noesel, Carel J. M. van

doi:10.1002/art.40756

Cited by 4 publications

(2 citation statements)

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“…[85][86][87] The precursors of these B cells in some autoimmune diseases are currently unknown, but experiments in which the somatic hypermutations were reverted to germline counterparts in recombinant antibodies expressed by expanded CD19 hi CD27 -CD21 -/lo B cells in SjS suggest that their unmutated precursors were already autoreactive. 87,92 Hence, the accumulation of CD19 hi CD27 − CD21 −/lo B cells in some autoimmune diseases may result from the activation of autoreactive naive B cells that escaped the impaired early B-cell tolerance in RA, SjS, and SLE. Of note, we did not observe an increase in CD19 hi CD27 − CD21 −/lo B cells in T1D patients, suggesting that selfantigens targeted in these autoimmune diseases may not trigger the expansion of these B cells or that their expansion is not sufficient to be detected systemically in patient's blood 45 and T-bet induced by IFNγ.…”

Section: Impaired E Arly B-cell Toler An Ce Checkp Oints Lik Ely Famentioning

confidence: 99%

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Meffre

O’Connor

2019

Immunological Reviews

109

100

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A role for B cells in autoimmune diseases is now clearly established both in mouse models and humans by successful treatment of multiple sclerosis and rheumatoid arthritis with anti-CD20 monoclonal antibodies that eliminate B cells. However, the underlying mechanisms by which B cells promote the development of autoimmune diseases remain poorly understood. Here, we review evidence that patients with autoimmune disease suffer from defects in early B-cell tolerance checkpoints and therefore fail to counterselect developing autoreactive B cells. These B-cell tolerance defects are primary to autoimmune diseases and may result from altered Bcell receptor signaling and dysregulated T-cell/regulatory T-cell compartment. As a consequence, large numbers of autoreactive naive B cells accumulate in the blood of patients with autoimmune diseases and may promote autoimmunity through the presentation of self-antigen to T cells. In addition, new evidence suggests that this reservoir of autoreactive naive B cells contains clones that may develop into CD27 − CD21 −/lo B cells associated with increased disease severity and plasma cells secreting potentially pathogenic autoantibodies after the acquisition of somatic hypermutations that improve affinity for self-antigens. K E Y W O R D Sautoantibodies, autoimmune disease, B-cell development, immune tolerance checkpoint

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Section: Impaired E Arly B-cell Toler An Ce Checkp Oints Lik Ely Famentioning

confidence: 99%

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Meffre

O’Connor

2019

Immunological Reviews

109

100

View full text Add to dashboard Cite

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“…Saadoun et al observed high frequencies of autoreactive and unresponsive CD21 − /low B cell populations that associated with lymphoproliferation in patients with primary of SS [ 13 ]. Glauzy et al also demonstrated that the frequency of CD21 − /low B cells was increased in the peripheral blood of 5 of 8 SS patients [ 14 ]. In our case, the ratio of CD21+ marginal zone B cells and switch memory B cells as well as PD-1+ of marginal cells and HLADR+ of switch memory B cells was far lower in the case than in the recovery group ( Figure 2 C).…”

Section: Discussionmentioning

confidence: 99%

Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report

et al. 2020

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The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients—health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren’s syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.

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Salivary Gland Mucosa‐Associated Lymphoid Tissue–Type Lymphoma From Sjögren’s Syndrome Patients in the Majority Express Rheumatoid Factors Affinity‐Selected for IgG

Bende

Janssen

Beentjes

et al. 2020

Arthritis & Rheumatology

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Objective Patients with Sjӧgren's syndrome ( SS ) have an increased risk of developing malignant B cell lymphomas, particularly mucosa‐associated lymphoid tissue ( MALT )–type lymphomas. We have previously shown that a predominant proportion of patients with SS ‐associated salivary gland MALT lymphoma express somatically hypermutated IgM with strong amino acid sequence homology with stereotypic rheumatoid factors ( RF s). The present study was undertaken in a larger cohort of patients with SS ‐associated MALT lymphoma to more firmly assess the frequency of RF reactivity and the significance of somatic IGV ‐region mutations for RF reactivity. Methods B cell antigen receptors ( BCR s) of 16 patients with SS ‐associated salivary gland MALT lymphoma were analyzed. Soluble recombinant IgM was produced of 12 MALT lymphoma samples, including 1 MALT lymphoma sample that expressed an IgM antibody fitting in a novel IGHV 3‐30 –encoded stereotypic IGHV subset. For 4 of the 12 IgM antibodies from MALT lymphoma samples, the somatically mutated IGHV and IGKV gene sequences were reverted to germline configurations. Their RF activity and binding affinity were determined by enzyme‐linked immunosorbent assay and surface plasmon resonance, respectively. Results Nine (75%) of the 12 IgM antibodies identified in patients with SS ‐associated salivary gland MALT lymphoma displayed strong monoreactive RF activity. Reversion of the IGHV and IGKV mutations to germline configuration resulted in RF affinities for IgG that were significantly lower for 3 of the 4 somatically mutated IgM antibodies. In stereotypic IGHV 3‐7 / IGKV 3‐15 –encoded RF s, a recurrent replacement mutation in the IGKV 3‐15 –third complementarity‐determining region was found to play a pivotal role in the affinity for IgG‐Fc. Conclusion A majority of patients with SS‐associated salivary gland MALT lymphoma express somatically mutated BCRs that are selected for monoreactive, high‐affinity binding of IgG‐Fc. These data underscore the notion that soluble IgG, most likely in immune complexes in inflamed tissue...

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Rheumatoid Factor Reactivity of Expanded CD21^−/low B Cells in Patients With Sjögren's Syndrome: Comment on the Article by Glauzy et al

Cited by 4 publications

References 10 publications

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report

Salivary Gland Mucosa‐Associated Lymphoid Tissue–Type Lymphoma From Sjögren’s Syndrome Patients in the Majority Express Rheumatoid Factors Affinity‐Selected for IgG

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Rheumatoid Factor Reactivity of Expanded CD21−/low B Cells in Patients With Sjögren's Syndrome: Comment on the Article by Glauzy et al

Cited by 4 publications

References 10 publications

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report

Salivary Gland Mucosa‐Associated Lymphoid Tissue–Type Lymphoma From Sjögren’s Syndrome Patients in the Majority Express Rheumatoid Factors Affinity‐Selected for IgG

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Rheumatoid Factor Reactivity of Expanded CD21^−/low B Cells in Patients With Sjögren's Syndrome: Comment on the Article by Glauzy et al