Atypical memory B cells contribute to heterogeneous vaccine responses in ocrelizumab-treated patients with multiple sclerosis
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Le résumé fourni par la source
Abstract Background and Objectives 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 variability remain incompletely understood. We performed a longitudinal analysis of B-cell subset dynamics and antigen-specific T cell responses in OCR-treated pwMS and healthy controls to determine how immune cell composition, timing of OCR infusion, and lymphocyte dynamics influence humoral response outcomes. Methods Based on post-vaccination anti-Spike IgG titers measured by multiplex bead immunoassay, pwMS were categorized as super-responders (SR), responders (R), or non-responders (NR). A 35-marker spectral flow cytometry panel was used to characterize T- and B-cell subsets longitudinally, at baseline and following stimulation with a SARS-CoV-2 peptide pool. Results CD4 + and CD8 + T cell populations were preserved across OCR-treated pwMS, and SARS-CoV-2-specific T cells remained detectable for more than 6 months after vaccination. In contrast, residual B-cell subset composition distinguished responders from non-responders. DN2-like B cells (CD19 + CD27-IgD-T-bet + CD11c + CXCR5-) persisted despite repeated OCR infusions and were enriched in SR compared with NR. Repletion of mature naïve B cells in peripheral blood correlated with time since last OCR infusion and with stronger humoral immune responses. Conclusions B-cell subsets that resist OCR-mediated depletion may contribute to vaccine responsiveness in OCR-treated pwMS. Altered repletion kinetics of naïve B cell subsets in non-responders suggest that specific B-cell populations may serve as predictive biomarkers of vaccine-induced humoral immunity, despite preserved T-cell responses.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Atypical memory B cells contribute to heterogeneous vaccine responses in ocrelizumab-treated patients with multiple sclerosis
- Date Crossref
- 04/11/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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NYU Langone Health Multiple Sclerosis Comprehensive Care Center pays non établi dans la noticeÉtablissement de santé
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New York University pays non établi dans la noticeUniversité ou école supérieure
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Multiple Sclerosis Center Of Northeastern New York pays non établi dans la noticeÉtablissement de santé
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NYU Grossman School of Medicine Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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NYU Langone Medical Center pays non établi dans la noticeÉtablissement de santé
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NYU Langone Vaccine Center and Department of Medicine pays non établi dans la noticeOrganisation à but non lucratif
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Inc. Genentech pays non établi dans la noticeEntreprise
Multiple Sclerosis Comprehensive Care Center — NYU Langone Health, New York University et Multiple Sclerosis Center Of Northeastern New York, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.