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Publié dans: Nature Communications, 2024, 15, ⟨10.1038/s41467-024-47013-0⟩

Auteurs: Sara de Biasi, Domenico Lo Tartaro, Anita Neroni, Moritz Rau, Nikolaos Paschalidis, Rebecca Borella, Elena Santacroce, Annamaria Paolini, Lara Gibellini, Alin Liviu Ciobanu, Michela Cuccorese, Tommaso Trenti, Ignacio Rubio, Francesca Vitetta, Martina Cardi, Rafael José Argüello, Diana Ferraro, Andrea Cossarizza

Résumé

Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimodand natalizumab-treated patients, whose immune response differs from all the other MS treatments.

The immunosuppressive and immunomodulatory disease-modifying therapies (DMT) used for multiple sclerosis (MS) act at different levels, i.e., inhibiting the expansion of activated lymphocytes (teriflunomide), redirecting pathological immune cells away from the central nervous system [natalizumab, fingolimod (FTY)] or depleting immune cell subsets (B and T cells; anti-CD20, cladribine) 1 . In treated patients, DMT can introduce risk for increased infections, reduced vaccine effectiveness or reduce the duration of specific immunity. These aspects are of critical importance, especially in the course of a pandemic such as that due to SARS-CoV-2, where the host immune response is crucial 2-12 , and that was effectively fought by several different vaccines.

In patients with MS, DMT such as interferon (IFN)-β, glatiramer acetate and dimethyl fumarate (DMF) are not expected to compromise

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Lien vers le DOI – 10.1038/s41467-024-47013-0