Moreira Villanueva, AntíaMunteis Olivas, ElviraVera, AndreaMacías Gómez, AdriánBertrán Recasens, BernatRubio Pérez, Miguel AngelLlop, MireiaMartínez Rodríguez, Jose E.2022-09-162022-09-162022Moreira A, Munteis E, Vera A, Macías Gómez A, Bertrán Recasens B, Rubio Pérez MÁ, Llop M, Martínez-Rodríguez JE. Delayed B cell repopulation after rituximab treatment in multiple sclerosis patients with expanded adaptive natural killer cells. Eur J Neurol. 2022 Jul;29(7):2015-23. DOI: 10.1111/ene.153121351-5101http://hdl.handle.net/10230/54087Background and purpose: The aim was to evaluate whether adaptive NKG2C+ natural killer (NK) cells, characterized by enhanced antibody-dependent cell cytotoxicity (ADCC), may influence time to B cell repopulation after rituximab treatment in multiple sclerosis (MS) patients. Methods: This was a prospective observational study of MS patients treated with rituximab monitoring peripheral B cells for repeated doses. B cell repopulation was defined as CD19+ cells above 2% of total lymphocytes, classifying cases according to the median time of B cell repopulation as early or late (≤9 months, >9 months, respectively). Basal NK cell immunophenotype and in vitro ADCC responses induced by rituximab were assessed by flow cytometry. Results: B cell repopulation in 38 patients (24 relapsing-remitting MS [RRMS]; 14 progressive MS) was classified as early (≤9 months, n = 19) or late (>9 months, n = 19). RRMS patients with late B cell repopulation had higher proportions of NKG2C+ NK cells compared to those with early repopulation (24.7% ± 16.2% vs. 11.3% ± 10.4%, p < 0.05), and a direct correlation between time to B cell repopulation and percentage of NKG2C+ NK cells (R 0.45, p < 0.05) was observed. RRMS cases with late repopulation compared with early repopulation had a higher secretion of tumor necrosis factor α and interferon γ by NK cells after rituximab-dependent NK cell activation. The NK cell immunophenotype appeared unrelated to B cell repopulation in progressive MS patients. Conclusions: Adaptive NKG2C+ NK cells in RRMS may be associated with delayed B cell repopulation after rituximab, a finding probably related to enhanced depletion of B cells exerted by NK-cell-mediated ADCC, pointing to the use of personalized regimens with anti-CD20 monoclonal antibody therapy in some patients.application/pdfeng© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/ene.15312B cell repopulationNK cellsMultiple sclerosisRituximabinfo:eu-repo/semantics/openAccess