Compositional changes of B and T cell subtypes during fingolimod treatment in multiple sclerosis patients: a 12-month follow-up study

• Published in: PloS one Vol. 9; no. 10; p. e111115
• Main Authors: Claes, Nele, Dhaeze, Tessa, Fraussen, Judith, Broux, Bieke, Van Wijmeersch, Bart, Stinissen, Piet, Hupperts, Raymond, Hellings, Niels, Somers, Veerle
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Antigen presentation; Antigens; Apoptosis; B cells; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Biological response modifiers; Biology and Life Sciences; Biomedical research; Blood; Blood circulation; CD80 antigen; CD86 antigen; Cytometry; Data analysis; Female; Fingolimod Hydrochloride; Flow cytometry; Follow-Up Studies; Homeostasis; Humans; Immune response; Immunological memory; Immunology; Immunoregulation; Immunosuppressive Agents - therapeutic use; Interferon; Leukocyte migration; Life sciences; Long term effects; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medical research; Medicine and Health Sciences; Memory; Memory cells; Middle Aged; Motor vehicle driving; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; Neurosciences; NMR; Nuclear magnetic resonance; Pathogenesis; Patients; Peripheral blood; Propylene Glycols - therapeutic use; Rehabilitation; Sphingosine - analogs & derivatives; Sphingosine - therapeutic use; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Young Adult; Belgium; Netherlands
• DOI: 10.1371/journal.pone.0111115
• ISSN: 1932-6203

The long term effects of fingolimod, an oral treatment for relapsing-remitting (RR) multiple sclerosis (MS), on blood circulating B and T cell subtypes in MS patients are not completely understood. This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes. Furthermore, expression of surface molecules involved in antigen presentation and costimulation during fingolimod treatment are assessed in MS patients in a 12 month follow-up study. Using flow cytometry, B and T cell subtypes, and their expression of antigen presentation, costimulation and migration markers were measured during a 12 month follow-up in the peripheral blood of MS patients. Data of fingolimod-treated MS patients (n = 49) were compared to those from treatment-naive (n = 47) and interferon-treated (n = 27) MS patients. In the B cell population, we observed a decrease in the proportion of non class-switched and class-switched memory B cells (p<0.001), both implicated in MS pathogenesis, while the proportion of naive B cells was increased during fingolimod treatment in the peripheral blood (PB) of MS patients (p<0.05). The remaining T cell population, in contrast, showed elevated proportions of memory conventional and regulatory T cells (p<0.01) and declined proportions of naive conventional and regulatory cells (p<0.05). These naive T cell subtypes are main drivers of MS pathogenesis. B cell expression of CD80 and CD86 and programmed death (PD) -1 expression on circulating follicular helper T cells was increased during fingolimod follow-up (p<0.05) pointing to a potentially compensatory mechanism of the remaining circulating lymphocyte subtypes that could provide additional help during normal immune responses. MS patients treated with fingolimod showed a change in PB lymphocyte subtype proportions and expression of functional molecules on T and B cells, suggesting an association with the therapeutic efficacy of fingolimod.