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
| Autor: | Helen A. Papadaki, George Bertsias, Eva D. Papadimitraki, Prodromos Sidiropoulos, Amalia Raptopoulou, Dimitrios T. Boumpas, Magda Nakou, Georgios Katsikas, Helen Koutala, Herakles Kritikos |
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| Jazyk: | angličtina |
| Předmět: |
Male
T-Lymphocytes Antigens CD19 Immunology B-Lymphocyte Subsets Arthritis Bone Marrow Cells Pharmacology Lymphocyte Activation CD19 Arthritis Rheumatoid Antibodies Monoclonal Murine-Derived Antigen Rheumatology immune system diseases hemic and lymphatic diseases medicine Humans Immunology and Allergy IL-2 receptor B-Lymphocytes biology business.industry Antibodies Monoclonal HLA-DR Antigens Middle Aged Flow Cytometry medicine.disease medicine.anatomical_structure Antirheumatic Agents Rheumatoid arthritis biology.protein Female Rituximab Bone marrow Antibody business Immunologic Memory Research Article medicine.drug |
| Zdroj: | Arthritis Research & Therapy |
| ISSN: | 1478-6354 |
| DOI: | 10.1186/ar2798 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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