B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis

Rapetti, Laetitia; Chavele, Konstantia-Maria; Evans, Catherine J; Ehrenstein, Michael R.

doi:10.1136/annrheumdis-2013-204049

Cited by 33 publications

(18 citation statements)

References 49 publications

(58 reference statements)

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“…The increased TACI and CD95 MFI values detected after treatment with TNF-inhibitors might suggest an inhibition of B cell activation [ 56 , 57 ]. Recent reports indicate that TNF-inhibitors modulate Fas-mediated apoptosis in RA [ 13 , 58 ] and it has been demonstrated that anti-TNF treatment in RA inhibits B cell function by disrupting germinal centre reactions [ 14 , 33 ] and decreasing T-cell dependent humoral responses [ 14 ]. B cell trafficking into inflamed tissues in RA is regulated by TNF and can be modulated not only by TNF-inhibitors [ 16 , 59 , 60 ], but also by tocilizumab treatment [ 61 ].…”

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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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%

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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“…However, we speculate that the mechanism by which CSA enhanced Ab production here may be indirect and via induction of Treg cells. There are contradictory reports of Treg effects on B cell function; that is, there may be suppression of B cells in one circumstance (101)(102)(103), but help for B cells in another (104)(105)(106). Help for B cells might be a consequence of IL-10 production by induced Treg cells.…”

Section: Discussionmentioning

confidence: 99%

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Zhou

Zhong

et al. 2016

The Journal of Immunology

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Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

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“…The increased TACI and CD95 MFI values detected after treatment with TNF-inhibitors might suggest an inhibition of B cell activation [56,57]. Recent reports indicate that TNF-inhibitors modulate Fasmediated apoptosis in RA [13,58] and it has been demonstrated that anti-TNF treatment in RA (ERA) and established RA patients under methotrexate treatment by ELISA. The effect of TNF-inhibitors and tocilizumab treatment in the production of these serological markers was also assessed in established RA patients at baseline and after an average of 8 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

01.06 B-cell phenotype and igd-cd27- memory b cells are affected by tnf-inhibitors and tocilizumab treatment in rheumatoid arthritis

Moura

Quaresma

Vieira

et al. 2017

Crossroads in Innate and Adaptive Immunity

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B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis

Cited by 33 publications

References 49 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

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

01.06 B-cell phenotype and igd-cd27- memory b cells are affected by tnf-inhibitors and tocilizumab treatment in rheumatoid arthritis

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