Peripheral B‐cell dysregulation is associated with relapse after long‐term quiescence in patients with multiple sclerosis. Issue 6 (12th May 2022) - Marsh‐Wakefield, Felix
Abstract: B cells play a major role in multiple sclerosis (MS), with many successful therapeutics capable of removing them from circulation. One such therapy, alemtuzumab, is thought to reset the immune system without the need for ongoing therapy in a proportion of patients. The exact cells contributing to disease pathogenesis and quiescence remain to be identified. We utilized mass cytometry to analyze B cells from the blood of patients with relapse‐remitting MS (RRMS) before and after alemtuzumab treatment, and during relapse. A complementary RRMS cohort was analyzed by single‐cell RNA sequencing. The R package "Spectre" was used to analyze these data, incorporating FlowSOM clustering, sparse partial least squares‐discriminant analysis and permutational multivariate analysis of variance. Immunoglobulin (Ig)A + and IgG1 + B‐cell numbers were altered, including higher IgG1 + B cells during relapse. B‐cell linker protein (BLNK), CD40 and CD210 expression by B cells was lower in patients with RRMS compared with non‐MS controls, with similar results at the transcriptomic level. Finally, alemtuzumab restored BLNK, CD40 and CD210 expression by IgA + and IgG1 + B cells, which was altered again during relapse. These data suggest that impairment of IgA + and IgG1 + B cells may contribute to MS pathogenesis, which can be restored by alemtuzumab. Abstract : B cells play an important role in the pathogenesis of multiple sclerosis (MS). We undertook a high‐dimensional analysis of B cell subsets in MS patients after treatment with alemtuzumab. Our investigation found IgA + and IgG1 + B cells were dysregulated in relapsing MS patients.