Résumé
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 \textgreater/=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.