A1.12 B-cell markers expression is affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis
2015
Background and objectives B cells play several important roles in rheumatoid arthritis (RA) pathogenesis, namely through autoantibody production, antigen presentation and T cell activation. The use of immunosuppressive drugs such as TNF-inhibitors and/or Il-6 receptor antagonist, tocilizumab, in RA might affect the circulating numbers of B cells and their activation state. The main goal of this work was to study the effect of TNF-inhibitors and tocilizumab on B cell phenotype and gene expression before and after treatment. Materials and methods Blood samples were collected from established RA patients treated with TNF-inhibitors (n = 10) and tocilizumab (n = 9) before and after treatment, and from healthy donors (n = 15). B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed by real-time PCR on isolated B-cells. Results The frequency of circulating B cell subpopulations was similar between controls and established RA patients irrespective of treatment. The mean fluorescence intensity (MFI) of TACI, CXCR5 and HLA-DR expressed on CD19 + B-cells was significantly increased in TNF-treated patients when compared to controls. A significant decrease of CD86 and increase of CD95 MFI was observed in CD19 + B-cells after TNF treatment. In tocilizumab-treated patients, HLA-DR and TLR9 MFI were significantly increased in CD19 + B-cells when compared to controls. No significant differences were observed in BAFF-R, BCMA, IgM and CD69 MFI in both groups of patients compared to controls. BAFF-R, Bcl-2, β2-microglobulin, FcgR2A, TLR7 and TLR10 gene expression were significantly increased after treatment with TNF and/or tocilizumab in comparison with controls, but no significant differences were observed when comparing baseline and follow-ups. Conclusions In RA, the use of TNF-inhibitors and/or tocilizumab treatment affects B-cell phenotype in circulation, but the effect of these drugs on B-cell gene expression is less evident. The decreased levels of CD86 expression and increased CD95 MFI on B-cells after TNF treatment support an inhibition of B-cell activation. Our results suggest that TNF-inhibitors and tocilizumab help to reduce B-cell infiltration in the joints and these activated B-cells express higher HLA-DR and CXCR5 levels in circulation.
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