Th1-CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis

Objective Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response. Methods We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response. Results The frequency of IFN-gamma(+) Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation-related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c(+) B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c(+) B cells would increase in response to exogenous IFN-gamma compared to IL-4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c(+) B cells takes place in patients with multiple sclerosis. Interestingly, CD11c(+) B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation. Interpretation Taken together, we postulate that Th1 cell - CD11c(+) B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595-611

Automated summary

This study found that the frequency of IFN-gamma(+) Th1 cells was persistently higher in plasma exchange responders compared to nonresponders. The frequency of Th1 cells before treatment was highly predictive of a beneficial response, with an AUC of 0.902. Plasma exchange treatment decreased inflammation-related gene expressions in Th1 cells and positively correlated with the frequency of CD11c(+) B cells.