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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

Magda Nakou1, Georgios Katsikas1, Prodromos Sidiropoulos1, George Bertsias1, Eva Papadimitraki1, Amalia Raptopoulou1, Helen Koutala2, Helen A Papadaki3, Herakles Kritikos1 and Dimitrios T Boumpas1*

Author Affiliations

1 Department of Rheumatology, Clinical Immunology and Allergy, University of Crete, Medical School, Voutes 71500, Heraklion, Greece

2 Laboratory of Flow Cytometry, University of Crete, Medical School, Voutes 71500, Heraklion, Greece

3 Department of Hematology, University of Crete, Medical School, Voutes 71500, Heraklion, Greece

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Arthritis Research & Therapy 2009, 11:R131  doi:10.1186/ar2798

See related editorial by Boumans and Tak,

Published: 28 August 2009



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.


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.


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.


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.