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

Abstract

Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some reports suggested that the therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets and elucidated B-cell-related biomarkers to predict the TNFi response. Peripheral B cells were analyzed for expression of CD19, CD27, CD38, and IgD in 31 healthy donors and 96 RA patients, including 21 who were followed 3 months after TNFi introduction. Treatment with steroids significantly altered the distribution of B-cell subsets. After adjustment for age, gender and steroid dose, patients with RA had similar B-cell subset proportions as controls. B-cell subset distribution did not differ by use of TNFi at baseline or before and after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportion 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) of responding to TNFi treatment. CD27+ cells produced 3 times more TNFalpha than did naive B cells, and were correlated with interferon-gamma produced from CD4+ cells in patients without TNFi treatment. 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 cell type 1 pathwa