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

Claes N, Dhaeze T, Fraussen J, Broux B, Van Wijmeersch B, Stinissen P, Hupperts R, Hellings N, Somers V - PLoS ONE (2014)

Bottom Line: This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes.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).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.

View Article: PubMed Central - PubMed

Affiliation: Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.

ABSTRACT

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.

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.

Results: 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.

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.

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Related in: MedlinePlus

Percentage of TFH and expression of CXCR5 and PD-1 during fingolimod treatment in MS patients.(A.) Percentage of PB follicular helper T cells (TFH) in MS patients treated with fingolimod. Data are presented as percentage within the CD4+ T cell population. (B.) Expression of CXCR5 and (C.) expression of PD-1 within TFH cell population.
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pone-0111115-g004: Percentage of TFH and expression of CXCR5 and PD-1 during fingolimod treatment in MS patients.(A.) Percentage of PB follicular helper T cells (TFH) in MS patients treated with fingolimod. Data are presented as percentage within the CD4+ T cell population. (B.) Expression of CXCR5 and (C.) expression of PD-1 within TFH cell population.

Mentions: The percentage of TFH (CD4+CD25-CD127+CXCR5+PD-1+) remained stable within the CD4+ population during fingolimod treatment (figure 4A, table S1).


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

Claes N, Dhaeze T, Fraussen J, Broux B, Van Wijmeersch B, Stinissen P, Hupperts R, Hellings N, Somers V - PLoS ONE (2014)

Percentage of TFH and expression of CXCR5 and PD-1 during fingolimod treatment in MS patients.(A.) Percentage of PB follicular helper T cells (TFH) in MS patients treated with fingolimod. Data are presented as percentage within the CD4+ T cell population. (B.) Expression of CXCR5 and (C.) expression of PD-1 within TFH cell population.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215872&req=5

pone-0111115-g004: Percentage of TFH and expression of CXCR5 and PD-1 during fingolimod treatment in MS patients.(A.) Percentage of PB follicular helper T cells (TFH) in MS patients treated with fingolimod. Data are presented as percentage within the CD4+ T cell population. (B.) Expression of CXCR5 and (C.) expression of PD-1 within TFH cell population.
Mentions: The percentage of TFH (CD4+CD25-CD127+CXCR5+PD-1+) remained stable within the CD4+ population during fingolimod treatment (figure 4A, table S1).

Bottom Line: This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes.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).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.

View Article: PubMed Central - PubMed

Affiliation: Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.

ABSTRACT

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.

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.

Results: 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.

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.

Show MeSH
Related in: MedlinePlus