SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells
Sara De Biasi,
Alin Liviu Ciobanu,
Elena Santacroce,
Domenico Lo Tartaro,
Gianluca Degliesposti,
Miriam D’Angerio,
Maristella Leccese,
Martina Cardi,
Tommaso Trenti,
Michela Cuccorese,
Lara Gibellini,
Diana Ferraro,
Andrea Cossarizza
Affiliations
Sara De Biasi
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Alin Liviu Ciobanu
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Elena Santacroce
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Domenico Lo Tartaro
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Gianluca Degliesposti
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Miriam D’Angerio
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Maristella Leccese
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Martina Cardi
AOU Policlinico di Modena, Neurology Unit, Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, 41124 Modena, Italy
Tommaso Trenti
AOU Policlinico di Modena, Diagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, 41124 Modena, Italy
Michela Cuccorese
AOU Policlinico di Modena, Diagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, 41124 Modena, Italy
Lara Gibellini
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Diana Ferraro
AOU Policlinico di Modena, Neurology Unit, Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, 41124 Modena, Italy
Andrea Cossarizza
Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are largely used in the treatment of both relapsing remitting (RR) and progressive (PR) forms of MS. Although effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and a high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality; this, however, suggested the presence of differences in immune responses driven by age and disease severity.