Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response

INTRODUCTION: Bone marrow (BM) is an immunologically privileged site where activated autoantibody-producing B cells may survive for prolonged periods. We investigated the effect of rituximab (anti-CD20 mAb) in peripheral blood (PB) and BM B-cell and T-cell populations in active rheumatoid arthritis (RA) patients. METHODS: Active RA patients received rituximab (1,000 mg) on days 1 and 15. PB (n = 11) and BM (n = 8) aspirates were collected at baseline and at 3 months. We assessed B-cell and T-cell populations using triple-color flow cytometry. RESULTS: Rituximab therapy decreased PB (from a mean 2% to 0.9%, P = 0.022) but not BM (from 4.6% to 3.8%, P = 0.273) CD19(+ )B cells, associated with a significant reduction in the activated CD19(+)HLA-DR(+ )subset both in PB (from 55% to 19%, P = 0.007) and in BM (from 68% to 19%, P = 0.007). Response to rituximab was preceded by a significant decrease in PB and BM CD19(+)CD27(+ )memory B cells (P = 0.022). These effects were specific to rituximab since anti-TNF therapy did not reduce total or activated B cells. Rituximab therapy did not alter the number of activated CD4(+)HLA-DR(+ )and CD4(+)CD25(+ )T cells. CONCLUSIONS: Rituximab therapy preferentially depletes activated CD19(+)HLA-DR(+ )B cells in the PB and BM of active RA patients. Clinical response to rituximab is associated with depletion of CD19(+)CD27(+ )memory B cells in PB and BM of RA patients.