Journal Article

Compositional Changes of B and T Cell Subtypes during Fingolimod Treatment in Multiple Sclerosis Patients: A 12-Month Follow-Up Study

Broux, Bieke, Van Wijmeersch, Bart, Dhaeze, Tessa, Stinissen, Piet, Hupperts, Raymond, Hellings, Niels, Somers, Veerle, Fraussen, Judith, Claes, Nele

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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