Artikel
NK cells from patients with rheumatic disease specifically react in response to rituximab
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Autoren
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Wolfgang Merkt
- Universitätsklinikum Heidelberg, Medizinische Klinik V, Sektion Rheumatologie, Heidelberg
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Shuyang Zhao
- Universitätsklinikum Heidelberg, Medizinische Klinik V, Sektion Rheumatologie, Heidelberg
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Norbert Blank
- Abteilung für Rheumatologie, Uniklinik Heidelberg, Heidelberg
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Carsten Watzl
- Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Immunologie, Dortmund
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Hanns-Martin Lorenz
- Universitätsklinikum Heidelberg, Medizinische Klinik V, Sektion Rheumatologie, Heidelberg
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
Text
Background: The monoclonal anti-CD20 antibody rituximab is successfully used in the treatment of numerous rheumatic diseases. In vivo, rituximab leads to the depletion of B lymphocytes. Natural killer (NK) cells can kill rituximab-coated tumor cells [1]. Using an NK cell depletion and re-substitution approach, we have recently shown that NK cells can also lyse rituximab-coated healthy B lymphocytes in vitro [2]. This evidence is lacking in rheumatic diseases.
Objective: We wanted to know whether NK cells can also lyse rituximab-coated B lymphocytes from patients with rheumatic disease.
Methods: We used granulomatosis with polyangiitis (GPA) as a model of rheumatic disease. Peripheral blood mononuclear cells (PBMCs) were cultured overnight in the presence of saturated doses of rituximab, control monoclonal anti-TNFα antibody infliximab, a monoclonal anti-CD16 antibody or without any antibody. Cells were analyzed by 7-color flow cytometry. Exploratory statistical analyses were performed.
Results: RTX depleted B cells in PBMCs from GPA patients in absence of complement factors. RTX induced degranulation and distinct phenotypic changes of NK cells. These findings were similar to those in healthy individuals [2], but depended on the presence of B lymphocytes. This is strongly indicative of killing of rituximab-coated B lymphocytes by NK cells, also in GPA.
Conclusion: These data show that NK cells from patients with rheumatic disease specifically react in response to rituximab in vitro. NK cells may therefore be involved in the mechanisms of action of rituximab in these conditions.
References
- 1.
- Rudnicka D, Oszmiana A, Finch DK, Strickland I, Schofield DJ, Lowe DC, Sleeman MA, Davis DM. Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity. Blood. 2013 Jun 6;121(23):4694-702. DOI: 10.1182/blood-2013-02-482570
- 2.
- Merkt W, Lorenz HM, Watzl C. Rituximab induces phenotypical and functional changes of NK cells in a non-malignant experimental setting. Arthritis Res Ther. 2016;18:206.
