Chronic signs of memory B cell activation in patients with Behçet’s disease are partially restored by anti-tumour necrosis factor treatment

Houwen, Tim B. van der; Hagen, P. Martin van; Timmermans, Wilhemina M. C.; Bartol, Sophinus J. W.; Lam, King H.; Kappen, Jasper H; Zelm, Menno C. van; Laar, Jan A. M. van

doi:10.1093/rheumatology/kew366

Cited by 13 publications

(8 citation statements)

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“…The disparities found between studies could be related to the use of different anti-TNF agents, disease activity, cohort size and previous treatments administrated to RA patients. Previous works have demonstrated that TNF-inhibitors affect memory B cell subpopulations not only in RA, but also in other inflammatory diseases [ 16 , 19 , 31 , 36 – 39 ]. In fact, circulating naive B cells and class-switched memory B cells were found to be normally present in peripheral blood of patients with Crohn’s disease, whereas IgM+ memory B cell numbers were reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Also, it has been shown that in patients with sarcoidosis, the increased blood levels of CD27-IgA+ memory B cells are normalized after treatment with infliximab [ 37 ]. Furthermore, it has been recently demonstrated that patients with Behçet's disease have significantly lower memory B cell numbers in peripheral blood, particularly CD27+IgA+ B cells, when compared to controls, but treatment with adalimumab restored to normal levels blood B cell numbers [ 39 ]. Of note, it has been previously shown that established RA patients have significantly lower levels of peripheral blood pre-switch IgD+CD27+ memory B cells when compared to healthy individuals, but treatment with infliximab restored the frequency of this B cell subpopulation to normal levels [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

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B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis

et al. 2017

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BackgroundThe use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA.MethodsBlood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterized by flow cytometry and B-cell gene expression was analyzed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA.ResultsThe frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/ or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab.ConclusionsIn RA patients, the use of TNF-inhibitors and/ or tocilizumab treatment affects B-cell phenotype and IgD-CD27- memory B cells in circulation, but not B-cell gene expression levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis

et al. 2017

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“…The exact causes of Behçet's disease (BD) are still unknown, and current knowledge suggested that BD could follow an autoimmune process induced by an infectious or environmental agent in genetically predisposed individuals. The major pathogenetic mechanisms underlying BD were linked to hyperactivity of neutrophils, gammadelta T (γδ T) lymphocytes, Th1 and Th17 lymphocytes, and down-regulation of regulatory T lymphocytes (Tregs) in the innate immunity system, and these have caused critical overproduction of proinflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-17 (10). However, growing evidence has suggested that B cells might also play a more eminent role in BD, which was not only responsible for antibody production but also involved in antigen presentation, pro-inflammatory cytokine secretion, and modulation of T cell activation.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease

Zhao

Duan

et al. 2021

Front. Neurol.

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Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.

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“…The broad spectrum of symptoms that are alleviated by treatment with anti-TNF-α agents confirms the major role of TNF-α in the diverse manifestations of BD. Blocking of TNF-α downregulates pro-inflammatory T-cell subsets and restores the memory B-cell compartment [66][67][68]. Next to the immunologic effects of anti-TNF-α treatment, the beneficial effect on vascular BD disease suggests an effect on the vascular endothelial cells, but this is not yet evidenced in BD.…”

Section: Discussionmentioning

confidence: 99%

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

Houwen

Laar

2020

IJMS

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In this both narrative and systematic review, we explore the role of TNF-α in the immunopathogenesis of Behçet’s disease (BD) and the effect of treatment with TNF-α blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-α may play a key role. In the narrative review, we report an increased production of TNF-α, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1β and IFN-γ. The abundance of TNF-α is found in both serum and in sites of inflammation. This increased presence of TNF-α stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-α is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-α blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-α in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.

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Chronic signs of memory B cell activation in patients with Behçet’s disease are partially restored by anti-tumour necrosis factor treatment

Cited by 13 publications

References 32 publications

B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis

B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

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