ytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patient

Author(s):Show less -

Boldrini, Vinicius O. ^{[1, 2]} ; Marques, Ana M. ^[2] ; Quintiliano, Raphael P. S. ^[1] ; Moraes, Adriel S. ^[1] ; Stella, Carla R. A. V. ^{[3, 1]} ; Longhini, Ana Leda F. ^{[1, 4]} ; Santos, Irene ^[1] ; Andrade, Marilia ^[1] ; Ferrari, Breno ^[1] ; Damasceno, Alfredo ^[3] ; Carneiro, Rafael P. D. ^{[1, 5]} ; Brandao, Carlos Otavio ^{[3, 1]} ; Farias, Alessandro S. ^{[6, 1, 2, 7]} ; Santos, Leonilda M. B. ^{[6, 1]}

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Neuroimmunol Unit, Campinas - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Autoimmune Res Lab, Campinas - Brazil

^[3] Univ Estadual Campinas, Dept Neurol, Campinas - Brazil

^[4] Univ Alabama Birmingham, Dept Immunol & Rheumatol, Birmingham, AL - USA

^[5] Irmandade Santa Casa Misericordia Sao Paulo, MS Clin Santa Casa Sao Paulo CATEM, Sao Paulo - Brazil

^[6] Natl Inst Sci & Technol Neuroimmunomodulat INCT N, Rio De Janeiro - Brazil

^[7] Expt Med Res Cluster EMRC, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 13, FEB 7 2022.
• Web of Science Citations: 0

Abstract

BackgroundEmerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) pathogenesis. ObjectiveTo investigate whether CD19(+) B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8(+) T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients. MethodsIn this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses. ResultsRRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8(+)GzmB(+) T lymphocytes when compared to healthy volunteers. An increase in circulating CD19(+)GzmB(+) B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-beta (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8(+) T lymphocytes, the expression of GzmB was significantly higher in CD19(+)Runx3(+)-expressing B cells when compared to CD19(+)Runx3(-) counterparts in RRMS patients. ConclusionsCD19(+) B cells may exhibit cytotoxic behavior resembling CD8(+) T lymphocytes in MS patients during different treatments. In the future, monitoring ``cytotoxic{''} subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions. (AU)

• FAPESP's process: 19/16116-4 - Ontogeny of pathogenic CD4 T cells during the initial neuroinflammation in Experimental Autoimmune Encephalomyelitis
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/21363-5 - Regulation of JAK/STAT/SOCS in the ontogen of IFNg-producing cells derivated from encephalitogenic Th17 cells during the clinical evolution of experimental autoimmune encephalomyelitis
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/26431-0 - Multiple sclerosis, clinical study, neuropsychological, immunological, biomarkers and modifying-disease new drugs
• Grantee: Leonilda Maria Barbosa dos Santos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/22052-8 - Role of Runx3 in the regulatory mechanism of effector profile of TCD4+ encephalitogenic lymphocytes in experimental autoimmune encephalomyelitis
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Multi-user Equipment Program