Background The 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.
Objectives 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.
Methods Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate (MTX) 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.
Results The frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment. However, established RA patients under MTX treatment had significantly increased frequencies of double negative (IgD-CD27-) B cells in comparison with controls. Treatment with TNF-inhibitors and tocilizumab did not affect the circulating levels of B-cell subpopulations. CD86 and CD95 had, respectively, a significantly lower and higher expression on B-cells after anti-TNF treatment. HLA-DR MFI values were also significantly increased in RA patients after treatment with TNF antagonists and tocilizumab. BAFF-R, TACI, BCMA, CD69, CXCR5, TLR9, IgM and CD5 expression on B cells were not significantly affected by TNF-inhibitors and tocilizumab. In addition, 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 under MTX treatment when compared to controls, but no significant differences were observed after anti-TNF and tocilizumab treatments when comparing baseline and follow-ups. Moreover, CXCL13 and sCD23, but not BAFF serum levels were significantly increased since early RA, but no effect of TNF-inhibitors and tocilizumab treatment was observed.
Conclusions In RA patients, the use of TNF-inhibitors and/or tocilizumab treatment affects B-cell phenotype in circulation, but not B-cell frequencies or B-cell gene expression. Our results suggest that TNF-inhibitors and tocilizumab help to reduce B-cell infiltration in inflammatory sites, allowing these activated B-cells to recirculate through blood and lymphatic systems.
Disclosure of Interest None declared
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