Compositional Changes of B and T Cell Subtypes during Fingolimod Treatment in Multiple Sclerosis Patients: A 12-Month Follow-Up Study |
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| Authors: | Nele Claes Tessa Dhaeze Judith Fraussen Bieke Broux Bart Van Wijmeersch Piet Stinissen Raymond Hupperts Niels Hellings Veerle Somers |
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| Affiliation: | 1. Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.; 2. Rehabilitation & MS-Center, Overpelt, Belgium.; 3. Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.; 4. Department of Neurology, Orbis Medical Center, Sittard, The Netherlands.; University Hospital Basel, Switzerland, |
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| Abstract: | Background and objectiveThe 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.MethodsUsing 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.ResultsIn 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.ConclusionsMS 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. |
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