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.
Highlights
A complex interplay between T and B cells drives the disease course of multiple sclerosis (MS)
Lymphocytes cannot exit the lymph nodes into the circulation, leading to the entrapment of lymphocytes in lymphatic systems, causing lymphopenia in peripheral blood (PB) of treated patients, thereby reducing the number of inflammatory cells migrating to the central nervous system (CNS) [9,10,11,12]
To understand the longitudinal immunological effects of fingolimod treatment, we investigated the effect of this treatment on B and T cell subtypes and antigen presentation, costimulation and migration molecules expressed on these cells in PB of MS patients in a 12 months follow-up study
Summary
A complex interplay between T and B cells drives the disease course of multiple sclerosis (MS). T cells (CD4+CD25-CD127+) can drive the disease and regulatory T cells (CD4+CD25hiCD127lo) control immune homeostasis [1,2,3] Both within the conventional and regulatory T cell populations, naive (CD45RA+CD45RO-) and memory (CD45RA-CD45RO+). Migration of B and T cells is partly mediated via chemokine (C-X-C motif) receptor 5 (CXCR5) [4], Fingolimod is the FDA approved oral treatment for MS and has shown efficacy in relapsing remitting (RR) MS [5,6,7,8]. 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. 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
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