Постоянная классическая и нетипичная память B Клетки под гетерогенной вакцинной реакции в Оклелизумаб-Treated Multical Sclerosis.
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Curtin Ryan, Velmurugu Yogambigai, Dibba Fatoumatta, Hao Yuan, Sreenivasaiah Chaitra, Khodadadi-Jamayran Alireza, Nyovanie Samantha, Kim Angie, Samanovic Marie L, Mulligan Mark, Priest Jessica, Cabatingan Mark, Winger Ryan C, Patskovsky Yury, Kister Ilya, Silverman Gregg J, Krogsgaard Michelle
Аннотация
Оригинал публикации
Persistent Classical and Atypical Memory B Cells Underlie Heterogeneous Vaccine Responses in Ocrelizumab-Treated Multiple Sclerosis.
Patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR), a B-cell-depleting therapy, exhibit heterogeneous humoral responses to SARS-CoV-2 mRNA vaccination. The mechanisms underlying this heterogeneity remain poorly understood. We performed a longitudinal analysis of antigen-specific T and B cell responses in OCR-treated pwMS and non-MS healthy controls following vaccination. Based on post-vaccination anti-Spike IgG titers, pwMS were categorized as 'super-responders' (SR), 'responders' (R), or 'non-responders' (NR). We investigated how immune cell composition, timing of OCR infusion, and lymphocyte subset dynamics influenced humoral response outcomes. While CD4+ and CD8+ T cell populations were largely preserved across all OCR-treated pwMS, distinct differences in the representation of residual B cell composition distinguished responders from non-responders. Notably, CD19+CD27+ classical memory B cells and CD19+CD27-IgD-T-bet+CD11c+CXCR5-DN2-like B cells persisted following OCR infusion and were enriched in the SR group compared to the NR group. Our findings identify persistent memory B cell subsets that escape OCR depletion as key immune correlates and mechanistic mediators of vaccine responsiveness in OCR-treated pwMS, highlighting potential targets to enhance vaccine efficacy in this population. All participating patients were enrolled in clinical trials NCT04843774 and NCT04682548.