Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis

Background and purpose: Natural killer (NK) cells may play a role in multiple sclerosis (MS). Ratios of NK cells to CD4⁺ T cells have been proposed as a biomarker for the therapeutic effect of stem cell transplantation in MS. The objectives here were to explore the relevance of this ratio in MS patients by analysing NK and T cell subsets, as well as their prognostic value for disease activity. Methods: Baseline peripheral blood mononuclear cells of 50 relapsing–remitting MS patients, participating in our vitamin D supplementation study (SOLARIUM), were analysed with flow cytometry. Disease activity was measured as new magnetic resonance imaging lesions, relapses and mean plasma neurofilament light chain levels after 48 weeks of follow-up. Results: The proportion of NK cells correlated negatively with CD4⁺ T cells (R = −0.335, p = 0.001) and interleukin 17A (IL-17A⁺) CD4⁺ T cells (R = −0.203, p = 0.043). Participants with magnetic resonance imaging activity or relapses displayed lower NK/IL-17A⁺CD4⁺ T cell ratios (p =0.025 and p = 0.006, respectively). The NK/IL-17A⁺CD4⁺ T cell ratio correlated negatively with neurofilament light chain levels (R = −0.320, p = 0.050). Vitamin D supplementation did not affect these ratios. Conclusions: Our data suggest a protective role of an expanded NK cell compartment compared to the CD4⁺ T cell subset fractions in relapsing–remitting MS patients. NK/CD4⁺ T cell ratios may be a prognostic biomarker for disease activity in MS.