INTRODUCTION: Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets to elucidate B-cell-related biomarkers to predict the TNFi response. METHODS: Peripheral B cells were analyzed for expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96 RA patients, including 21 patients who were followed 3 months after TNFi initiation. RESULTS: Treatment with steroids significantly altered the distribution of B-cell subsets. After we adjusted for age, sex and steroid dose, we found that patients with RA had B-cell subset proportions similar to controls. B-cell subset distributions did not differ upon use of TNFi at baseline or before or after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportions of CD27(+) memory B cells at baseline, and >/=26% CD27(+) cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27(+) cells produced three times more TNFalpha than did TNFi-naive B cells and were correlated with interferon gamma produced from CD4(+) cells in patients without TNFi treatment. CONCLUSIONS: In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFalpha-dependent activation of the T helper type 1 cell pathway.
High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study
Daien, C. I.; Gailhac, S.; Mura, T.; Combe, B.; Hahne, M.; Morel, J.
Arthritis Res Ther
2014 / vol 16 / pages R95
10.1186/ar4543 ar4543 [pii]
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