Background and objectives B-cells play several important roles in rheumatoid arthritis (RA) pathogenesis, namely through autoantibody production, antigen presentation and T cell activation, but few studies have been performed in untreated early RA patients. Therefore, the main goal of this study was to characterise B-cell phenotype and B-cell gene expression levels since early RA onset in comparison with the chronic phase of the disease.
Materials and methods Blood samples were collected from untreated early RA (ERA) patients (<1 year of disease duration), established RA patients under methotrexate treatment and age and sex-matched healthy donors. B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed 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 patients’ groups, but established RA had significantly increased frequencies of double negative (IgD-CD27-) B-cells in comparison with controls. CXCR5 B-cell expression was significantly increased in both ERA and established RA in comparison with controls, but no significant differences were observed in BAFF-R, TACI, BCMA, CD69, CD86, HLA-DR, TLR9, CD95, IgM and CD5 B-cell expression between all groups analysed. Furthermore, alterations in B-cell gene expression levels were found in BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M in ERA and established RA patients when compared to controls, but no significant differences were detected in AID, BCMA, CXCR5, TLR7 and TLR10 B-cell gene expression between all groups. In addition, CXCL13 and sCD23, but not BAFF serum levels, were significantly increased since early RA.
Conclusions CXCR5 B-cell expression and CXCL13 serum levels are significantly increased in untreated early RA (<1 year of disease duration) and established RA patients when compared to controls, which supports B-cell activation and recruitment to inflammatory sites since early disease onset. Alterations in B-cell gene expression levels increase with disease progression, particularly in BAFF- and toll-like receptors. The augmented sCD23 serum levels detected in ERA patients suggest that B-cell maturation occurs from early RA onset.
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