Rheumatology Advance Access originally published online on May 30, 2006
Rheumatology 2007 46(1):29-36; doi:10.1093/rheumatology/kel148
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Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy
1Centre for Rheumatology and 2Department of Haematology, University College London, London, UK.
Correspondence to: Maria J. Leandro, University College London, Centre for Rheumatology, Windeyer Building, Room 317, 46 Cleveland Street, London W1T 4JF, UK. E-mail: maria.leandro{at}ucl.ac.uk
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Objective. To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy.
Methods. Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry.
Results. CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM.
Conclusion. In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low.
KEY WORDS: Rheumatoid arthritis, Rituximab, B-cell depletion, Bone marrow