Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 100, Issue 6, Pages 453-467Publisher
WILEY
DOI: 10.1111/imcb.12552
Keywords
Alemtuzumab; B cells; mass cytometry; multiple sclerosis
Categories
Funding
- International Society for the Advancement of Cytometry (ISAC) Marylou Ingram Scholars program
- Multiple Sclerosis Research Australia
- SanofiGenzyme
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B cells play a major role in multiple sclerosis (MS), and alemtuzumab therapy can restore B cell damage, which is of great significance in preventing the progression of the disease.
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 IgG(1)(+) B-cell numbers were altered, including higher IgG(1)(+) 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 IgG(1)(+) B cells, which was altered again during relapse. These data suggest that impairment of IgA(+) and IgG(1)(+) B cells may contribute to MS pathogenesis, which can be restored by alemtuzumab.
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