In: Arthritis Research & Therapy, 18 (2016), Nr. 206. pp. 1-11. ISSN 1478-6362
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Abstract
Background: Rituximab has broad and increasing application in rheumatic diseases. It is known from lymphoma studies that natural killer (NK) cells can lyse rituximab-coated transformed B cells. However, the role of NK cells in mediating rituximab-induced depletion of non-malignant B cells is unknown. The purpose of this study was to provide fundamental data on rituximab-mediated effects on NK cells in PBMCs without tumor cells, in order to simulate effects that could be relevant in patients with rheumatic disease. Methods: Freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured overnight with therapeutic antibodies. NK cells were isolated using a commercial kit or depleted from PBMCs using anti-CD56 and anti-CD16 monoclonal antibodies and magnetic beads. Cells were analyzed by multicolor flow cytometry. Cytotoxicity assays were performed using 51Cr-labeled K562 target cells. Results: Addition of rituximab to PBMCs resulted in depletion of B cells, which was dependent on NK cells and serum factors. The extent of B cell depletion correlated with the percentage of NK cells. Following incubation with rituximab, NK cells within PBMCs were activated, degranulated and downregulated the low affinitiy Fc-γ-receptor CD16 (FcγRIIIA). The co-activating receptor CD137 (41BB) was upregulated on a fraction of NK cells. NK cell function was altered in some donors in whom we observed rituximab-dependent reduction in NK cell cytotoxicity towards K562 tumor cells. Conclusions: NK cells mediate rituximab-induced B cell depletion. Rituximab induces altered NK cell phenotype and function.
Document type: | Article |
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Journal or Publication Title: | Arthritis Research & Therapy |
Volume: | 18 |
Number: | 206 |
Publisher: | BioMed Central |
Place of Publication: | London |
Date Deposited: | 20 Sep 2016 13:30 |
Date: | 2016 |
ISSN: | 1478-6362 |
Page Range: | pp. 1-11 |
Faculties / Institutes: | Medizinische Fakultät Heidelberg > Medizinische Universitäts-Klinik und Poliklinik |
DDC-classification: | 610 Medical sciences Medicine |