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

IntroductionBone marrow (BM) is an immunologically privileged stop where activated autoantibody-producing B cells may survive for prolonged periods. We investigated the corollary of rituximab (anti-CD20 mAb) in peripheral blood (PB) and BM B- and T-cell populations in active rheumatoid arthritis (RA) patients. Methods: Active RA patients received rituximab (1000mg) on days 1 and 15. PB (n=11) and BM (n=8) aspirates were collected at baseline and at 3 months. We assessed B- and T-cell populations using triple-color flow cytometry. Results: Rituximab therapy decreased PB (from a mean 2% to 0.9%, P=0.022) nevertheless not BM (from 4.6% to 3.8%, P=0.273) CD19+ B cells, associated with a expressing reduction in the activated CD19+ HLA-DR+ subset both in PB (from 55% to 19%, P=0.007) and BM (68% to 19%, P=0.007). Response to rituximab was preceded by a significant abbreviate in PB and BM CD19+ CD27+ memory B cells (P=0.022). These effects were particular to rituximab since anti-tumour necrosis factor (TNF) therapy did not decrease complete or activated B cells. Rituximab therapy did not convert 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+ cognizance B cells in PB and BM of RA patients.

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