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The main objective of this study was to find out if biological\/immune traits correlate with a beneficial response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of IFN\u2010\u03b3<jats:sup>+<\/jats:sup> 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\u2010related gene expressions in Th1 cells. Meanwhile, <jats:italic>IFNG<\/jats:italic> expression in Th1 cells positively correlated with the frequency of CD11c<jats:sup>+<\/jats:sup> B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c<jats:sup>+<\/jats:sup> B cells would increase in response to exogenous IFN\u2010\u03b3 compared to IL\u20104, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c<jats:sup>+<\/jats:sup> B cells takes place in patients with multiple sclerosis. Interestingly, CD11c<jats:sup>+<\/jats:sup> B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Taken together, we postulate that Th1 cell \u2010 CD11c<jats:sup>+<\/jats:sup> 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. 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