Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving anti-TNF therapy

Bankó, Zsuzsanna; Pozsgay, Judit; Gáti, Tamás; Rojkovich, Bernadette; Újfalussy, Ilona; Sármay, Gabriella

doi:10.1016/j.clim.2017.05.012

Cited by 26 publications

(18 citation statements)

References 39 publications

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“…Previous reports have indicated that anti-TNF treatment influences the expression of the costimulatory molecule, CD86, as well as that of the inhibitory receptor, Fcγ receptor IIb (FcγRIIb) (41), on B cells. Furthermore, our data corroborate with previous reports showing a decreased expression of activation marker CD69, along with an increase in regulatory B cells after ADA (42) and TCZ treatments (14), indicating that cytokine inhibition therapy can normalize peripheral B cells. In this regard, recent functional investigations of RA, SLE, and Sjögren's B cells have identified that particularly memory B cells from patients in an anergic or post-activated status demonstrate reduced B cell receptor responsiveness and cytokine production (43).…”

Section: Discussionsupporting

confidence: 92%

Therapeutic Cytokine Inhibition Modulates Activation and Homing Receptors of Peripheral Memory B Cell Subsets in Rheumatoid Arthritis Patients

et al. 2020

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Memory B cells have known to play an important role in the pathogenesis of rheumatoid arthritis (RA). With the emergence of B cell-targeted therapies, the modulation of memory B cells appears to be a key therapeutic target. Human peripheral memory B cells can be distinguished based on the phenotypic expression of CD27 and IgD, characterizing the three major B cell subpopulations: CD27+IgD+ pre-switch, CD27+IgD-post-switch, and CD27-IgD-double-negative memory B cells. We evaluated different memory cell populations for activation markers (CD95 and Ki-67) and chemokine receptors (CXCR3 and 4) expressing B cells in active RA, as well as under IL6-R blockade by tocilizumab (TCZ) and TNF-α blockade by adalimumab (ADA). Memory B cells were phenotypically analyzed from RA patients at baseline, week 12, and week 24 under TCZ or ADA treatment, respectively. Using flow cytometry, surface expression of CD95, intracellular Ki-67, and surface expressions of CXCR3 and CXCR4 were determined. Compared with healthy donors (n = 40), the phenotypic analysis of RA patients (n = 80) demonstrated that all three types of memory B cells were activated in RA patients. Surface and intracellular staining of B cells showed a significantly higher percentage of CD95+ (p < 0.0001) and Ki-67+ (p < 0.0001) cells, with numerically altered CXCR3+ and CXCR4+ cells in RA. CD95 and Ki-67 expressions were highest in post-switch memory B cells, whereas CD19+CXCR3+ and CD19+CXCR4+ expressing cells were substantially higher in the pre-switch compartment. In all subsets of the memory B cells, in vivo IL-6R, and TNF-α blockade significantly reduced the enhanced expressions of CD95 and Ki-67. Based on our findings, we conclude that the three major peripheral memory B cell populations, pre-, post-switch, and double-negative B cells, are activated in RA, demonstrating enhanced CD95 and Ki-67 expressions, and varied expression of CXCR3 and CXCR4 chemokine receptors when compared with healthy individuals. This activation can be efficaciously modulated under cytokine inhibition in vivo.

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Section: Discussionsupporting

confidence: 92%

Therapeutic Cytokine Inhibition Modulates Activation and Homing Receptors of Peripheral Memory B Cell Subsets in Rheumatoid Arthritis Patients

et al. 2020

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“…IL-10-producing B REGS were also found to be decreased in patients, and increased after therapy with MTX together with the anti-TNF-α agents, adalimumab or etanercept. 52 In this study, no significant differences in the frequencies of total memory (CD27+) and IgM memory (IgD+CD27+) B lymphocytes were observed. Only the subset of CD27+CD69+ B lymphocytes, the memory B cell subset with the early B cell activation marker CD69, was found increased in Rheumatoid arthritis patients versus controls and significantly decreased after treatment.…”

Section: Effects Of Anti-tnf-α Therapy On B Lymphocytes In Rheumatoidcontrasting

confidence: 54%

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti–TNF-α Agents on B Lymphocytes: A Review of the Literature

Pala

Diaz

Blomberg

et al. 2018

Clinical Therapeutics

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B lymphocytes play a significant role in the pathogenesis of rheumatoid arthritis, and B cell-depletion therapy has a major effect on the course of the disease. The advances in treatment of rheumatoid arthritis include the development of targeted therapies. Anti-TNF-α therapies are widely used despite potentially serious adverse events. The data on the effects of anti-TNF-α therapies on B lymphocytes are limited and conflicting. There is a need for larger studies to better understand the effects of newly discovered therapies on the different cells of the immune system.

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“…Several induction agents and cell therapies have been demonstrated to support Breg survival and induction in vivo in transplantation. Multiple immune modulators in the context of autoimmune disease also promote Breg, offering additional therapeutic candidates [97,98,127‐130]. Novel reagents in development may be able to soon offer specific Breg targeting.…”

Section: Introductionmentioning

confidence: 99%

Regulatory B cells in transplantation: roadmaps to clinic

et al. 2020

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Over the last two decades, an additional and important role for B cells has been established in immune regulation. Preclinical studies demonstrate that regulatory B cells (Breg) can prolong allograft survival in animal models and induce regulatory T cells. Operationally tolerant human kidney transplant recipients demonstrate B-cell-associated gene signatures of immune tolerance, and novel therapeutic agents can induce Bregs in phase I clinical trials in transplantation. Our rapidly expanding appreciation of this novel B-cell subtype has made the road to clinical application a reality. Here, we outline several translational pathways by which Bregs could soon be introduced to the transplant clinic.

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Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving anti-TNF therapy

Cited by 26 publications

References 39 publications

Therapeutic Cytokine Inhibition Modulates Activation and Homing Receptors of Peripheral Memory B Cell Subsets in Rheumatoid Arthritis Patients

Therapeutic Cytokine Inhibition Modulates Activation and Homing Receptors of Peripheral Memory B Cell Subsets in Rheumatoid Arthritis Patients

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti–TNF-α Agents on B Lymphocytes: A Review of the Literature

Regulatory B cells in transplantation: roadmaps to clinic

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