Peripheral blood T cell subset characteristics of multiple sclerosis in remission phase correlate with annualized relapse rates

Objective: A large number of disease-modifying drugs are available for multiple sclerosis (MS); however, there is no established biomarker to predict long-term disease severity and future relapses in MS. We aimed to clarify the alterations in peripheral blood T cell subsets that are associated with MS relapse and disease severity, according to cytokine production profiles in the remission phase. Methods: Blood samples collected from 29 relapsing–remitting MS patients in the remission phase and 21 healthy controls (HC) were analyzed for various cytokine-producing T cell subsets by flow cytometry. Results: MS patients in the remission phase had significantly higher percentages of interleukin (IL)-17+CD4+ T cells, IL-4+CD4+ T cells, IL-9+CD4+ T cells, interferon-γ+CD8+ T cells and IL-4+CD8+ T cells than HC (P = 0.047, P = 0.007, P = 0.026, P = 0.015 and P = 0.007, respectively). In MS, the percentages of IL-9+CD4+ T cells, IL-9+CD8+ T cells and IFN-γ+IL-17+CD8+ T cells showed a significant positive correlation with annualized relapse rates (ARR) (P = 0.011, r = 0.47, P = 0.007, r = 0.49 and P = 0.044, r = 0.38, respectively). Conclusions: In the remission phase of MS, both anti-inflammatory cytokine-producing T cells and pro-inflammatory cytokine-producing T cells are increased; however, only the percentages of pro-inflammatory cytokine-producing T cells, such as IL-9-producing CD4+ T cells, IL-9-producing CD8+ T cells and IFN-γ- and IL-17-producing CD8+ T cells, correlate with ARR. These pro-inflammatory cytokine-producing T cells in the remission phase might be candidate biomarkers for future relapses in MS patients.