Limits...
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.

Show MeSH

Related in: MedlinePlus

B cell expression levels of antigen presentation and costimulation molecules during fingolimod treatment.Mean fluorescence intensity (MFI) of (A) HLA-DR/DP/DQ, (B) CD80 and (C) CD86 expression within the B cell population from fingolimod-treated MS patients during follow-up.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4215872&req=5

pone-0111115-g003: B cell expression levels of antigen presentation and costimulation molecules during fingolimod treatment.Mean fluorescence intensity (MFI) of (A) HLA-DR/DP/DQ, (B) CD80 and (C) CD86 expression within the B cell population from fingolimod-treated MS patients during follow-up.

Mentions: During fingolimod treatment, both the percentage of HLA-DR/DP/DQ, CD80 and CD86 positive cells and the expression of these surface markers on CD19+ B cells was assessed using flow cytometric analysis. The percentage of HLA-DR/DP/DQ+ B cells (data not shown) and the expression of HLA-DR/DP/DQ (MFI) on B cells was significantly decreased after 3 m and 1 m of fingolimod treatment, respectively, in comparison with baseline (p<0.05; figure 3A; table S2). Fingolimod treatment resulted in an increased expression of both CD86 (after 1 m) and CD80 (after 3 m and 12 m) on B cells (MFI) compared with baseline (p<0.05; figure 3B and C; table S2). The percentages of CD80+ and CD86+ B cells remained stable during the follow-up period (table S2). Expression of antigen presentation and costimulation markers on B cells was comparable between baseline fingolimod and controls (table S2). Thus, the expression of HLA-DR/DP/DQ on PB B cells was decreased (both percentage of positive cells and MFI), while the expression of the costimulation molecules CD80 and CD86 (MFI) was increased during fingolimod treatment in MS patients.


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)

B cell expression levels of antigen presentation and costimulation molecules during fingolimod treatment.Mean fluorescence intensity (MFI) of (A) HLA-DR/DP/DQ, (B) CD80 and (C) CD86 expression within the B cell population from fingolimod-treated MS patients during follow-up.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111115-g003: B cell expression levels of antigen presentation and costimulation molecules during fingolimod treatment.Mean fluorescence intensity (MFI) of (A) HLA-DR/DP/DQ, (B) CD80 and (C) CD86 expression within the B cell population from fingolimod-treated MS patients during follow-up.
Mentions: During fingolimod treatment, both the percentage of HLA-DR/DP/DQ, CD80 and CD86 positive cells and the expression of these surface markers on CD19+ B cells was assessed using flow cytometric analysis. The percentage of HLA-DR/DP/DQ+ B cells (data not shown) and the expression of HLA-DR/DP/DQ (MFI) on B cells was significantly decreased after 3 m and 1 m of fingolimod treatment, respectively, in comparison with baseline (p<0.05; figure 3A; table S2). Fingolimod treatment resulted in an increased expression of both CD86 (after 1 m) and CD80 (after 3 m and 12 m) on B cells (MFI) compared with baseline (p<0.05; figure 3B and C; table S2). The percentages of CD80+ and CD86+ B cells remained stable during the follow-up period (table S2). Expression of antigen presentation and costimulation markers on B cells was comparable between baseline fingolimod and controls (table S2). Thus, the expression of HLA-DR/DP/DQ on PB B cells was decreased (both percentage of positive cells and MFI), while the expression of the costimulation molecules CD80 and CD86 (MFI) was increased during fingolimod treatment in MS patients.

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