Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and purpose</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>B cell repopulation in 38 patients (24 relapsing–remitting MS [RRMS]; 14 progressive MS) was classified as early (≤9 months, <jats:italic>n</jats:italic> = 19) or late (>9 months, <jats:italic>n</jats:italic> = 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%, <jats:italic>p</jats:italic> < 0.05), and a direct correlation between time to B cell repopulation and percentage of NKG2C+ NK cells (<jats:italic>R</jats:italic> 0.45, <jats:italic>p</jats:italic> < 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>