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Rituximab induces phenotypical and functional changes of NK cells in a non-malignant experimental setting

Merkt, Wolfgang ; Lorenz, Hanns-Martin ; Watzl, Carsten

In: Arthritis Research & Therapy, 18 (2016), Nr. 206. S. 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.

Dokumententyp: Artikel
Titel der Zeitschrift: Arthritis Research & Therapy
Band: 18
Nummer: 206
Verlag: BioMed Central
Ort der Veröffentlichung: London
Erstellungsdatum: 20 Sep. 2016 13:30
Erscheinungsjahr: 2016
ISSN: 1478-6362
Seitenbereich: S. 1-11
Institute/Einrichtungen: Medizinische Fakultät Heidelberg und Uniklinikum > Medizinische Universitäts-Klinik und Poliklinik
DDC-Sachgruppe: 610 Medizin
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