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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

Total number of lymphocytes, CD4+ T cells and CD19+ B cells in the PB.Total number (×103 cells/µl blood) of lymphocytes, T cells and B cells in treatment-naive, IFN-β treated MS patients at baseline and fingolimod-treated MS patients during 12 months follow-up. Mean and standard error of the mean are presented. • lymphocytes; ▪ CD4+ T cells; ▴ CD19+ B cells.
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pone-0111115-g001: Total number of lymphocytes, CD4+ T cells and CD19+ B cells in the PB.Total number (×103 cells/µl blood) of lymphocytes, T cells and B cells in treatment-naive, IFN-β treated MS patients at baseline and fingolimod-treated MS patients during 12 months follow-up. Mean and standard error of the mean are presented. • lymphocytes; ▪ CD4+ T cells; ▴ CD19+ B cells.

Mentions: In total, PB of 49 fingolimod-treated MS patients was collected at different time points up to 12 months of treatment. The cohort of fingolimod-treated MS patients was compared at baseline with 47 treatment-naive and 27 IFN-β treated MS patients (together referred to as controls). Fingolimod-treated MS patients at baseline and controls were comparable in terms of age, gender distribution and median EDSS score (table 1). Furthermore, no significant difference was observed in numbers of total lymphocytes, B cells or T cells (figure 1) between baseline fingolimod treatment and controls. For the MS patients receiving fingolimod treatment, pretreatment (baseline) values were used as reference to assess the effects of treatment. Five of 49 fingolimod-treated MS patients did not finish the study due to side effects caused by the treatment. Seven MS patients were excluded from the study as clinical non-responders, although no differences in T and B cell subtype proportions between non-responders and responders were found (data not shown).


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)

Total number of lymphocytes, CD4+ T cells and CD19+ B cells in the PB.Total number (×103 cells/µl blood) of lymphocytes, T cells and B cells in treatment-naive, IFN-β treated MS patients at baseline and fingolimod-treated MS patients during 12 months follow-up. Mean and standard error of the mean are presented. • lymphocytes; ▪ CD4+ T cells; ▴ CD19+ B cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111115-g001: Total number of lymphocytes, CD4+ T cells and CD19+ B cells in the PB.Total number (×103 cells/µl blood) of lymphocytes, T cells and B cells in treatment-naive, IFN-β treated MS patients at baseline and fingolimod-treated MS patients during 12 months follow-up. Mean and standard error of the mean are presented. • lymphocytes; ▪ CD4+ T cells; ▴ CD19+ B cells.
Mentions: In total, PB of 49 fingolimod-treated MS patients was collected at different time points up to 12 months of treatment. The cohort of fingolimod-treated MS patients was compared at baseline with 47 treatment-naive and 27 IFN-β treated MS patients (together referred to as controls). Fingolimod-treated MS patients at baseline and controls were comparable in terms of age, gender distribution and median EDSS score (table 1). Furthermore, no significant difference was observed in numbers of total lymphocytes, B cells or T cells (figure 1) between baseline fingolimod treatment and controls. For the MS patients receiving fingolimod treatment, pretreatment (baseline) values were used as reference to assess the effects of treatment. Five of 49 fingolimod-treated MS patients did not finish the study due to side effects caused by the treatment. Seven MS patients were excluded from the study as clinical non-responders, although no differences in T and B cell subtype proportions between non-responders and responders were found (data not shown).

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