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

作者：Claes Nele; Dhaeze Tessa; Fraussen Judith; Broux Bieke; Van Wijmeersch Bart; Stinissen Piet; Hupperts Raymond; Hellings Niels; Somers Veerle^*

来源：PLos One, 2014, 9(10): e111115.

DOI：10.1371/journal.pone.0111115

Background and objective: 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. %26lt;br%26gt;Methods: 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. %26lt;br%26gt;Results: In the B cell population, we observed a decrease in the proportion of non class-switched and class-switched memory B cells (p%26lt;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%26lt;0.05). The remaining T cell population, in contrast, showed elevated proportions of memory conventional and regulatory T cells (p%26lt;0.01) and declined proportions of naive conventional and regulatory cells (p%26lt;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%26lt;0.05) pointing to a potentially compensatory mechanism of the remaining circulating lymphocyte subtypes that could provide additional help during normal immune responses. %26lt;br%26gt;Conclusions: 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.

• 出版日期2014-10-31