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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

Proportional B cell and T cell subtype changes in MS patients during fingolimod treatment.(A) CD19+ B cell subtype proportion and (B) CD4+ T cell subtype proportion within the PB of treatment-naive, IFN-β and fingolimod-treated MS patients. Results are presented as relative values within the CD19+ B cell or CD4+ T cell population. Subtype proportions were calculated as follows: (% subtype/100)×% CD19+ or CD4+ within the total lymphocyte population. Statistically significant differences compared to 0 m are shown in bold. For B cells: naive B cells; NCSM B cells  =  non class-switched memory B cells; CSM B cells  =  class-switched memory B cells and DN B cells  =  double negative B cells. For T cells: nTreg  =  naive Treg; mTreg  =  memory Treg; TransTreg  =  transitional Treg; nTconv  =  naive Tconv; mTconv  =  memory Tconv; TransTconv  =  transitional Tconv.
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pone-0111115-g002: Proportional B cell and T cell subtype changes in MS patients during fingolimod treatment.(A) CD19+ B cell subtype proportion and (B) CD4+ T cell subtype proportion within the PB of treatment-naive, IFN-β and fingolimod-treated MS patients. Results are presented as relative values within the CD19+ B cell or CD4+ T cell population. Subtype proportions were calculated as follows: (% subtype/100)×% CD19+ or CD4+ within the total lymphocyte population. Statistically significant differences compared to 0 m are shown in bold. For B cells: naive B cells; NCSM B cells  =  non class-switched memory B cells; CSM B cells  =  class-switched memory B cells and DN B cells  =  double negative B cells. For T cells: nTreg  =  naive Treg; mTreg  =  memory Treg; TransTreg  =  transitional Treg; nTconv  =  naive Tconv; mTconv  =  memory Tconv; TransTconv  =  transitional Tconv.

Mentions: Although B cell numbers were reduced in the PB after fingolimod treatment, we investigated the effects of fingolimod treatment on the remaining B cell population in the PB of treated patients. Both non class-switched (CD19+IgD+CD27+) and class-switched memory B cells (CD19+IgD-CD27+) were significantly decreased in the peripheral B cell population from 3 m until end of follow-up (p<0.001; figure 2A, table S1, figure S1). In contrast, the percentage of CD19+IgD-CD27- cells (double negative B cells) was significantly increased within the B cell population at 1 m up to 12 m (p<0.05 at 1 m; p<0.001 at 3–12 m; figure 2A, table S1, figure S1). Naive B cells (CD19+IgD+CD27-) made up about 50% of the remaining peripheral B cells and the proportion of these cells was increased after 3 m fingolimod until end of follow-up (p<0.03; figure 2A; table S1, figure 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)

Proportional B cell and T cell subtype changes in MS patients during fingolimod treatment.(A) CD19+ B cell subtype proportion and (B) CD4+ T cell subtype proportion within the PB of treatment-naive, IFN-β and fingolimod-treated MS patients. Results are presented as relative values within the CD19+ B cell or CD4+ T cell population. Subtype proportions were calculated as follows: (% subtype/100)×% CD19+ or CD4+ within the total lymphocyte population. Statistically significant differences compared to 0 m are shown in bold. For B cells: naive B cells; NCSM B cells  =  non class-switched memory B cells; CSM B cells  =  class-switched memory B cells and DN B cells  =  double negative B cells. For T cells: nTreg  =  naive Treg; mTreg  =  memory Treg; TransTreg  =  transitional Treg; nTconv  =  naive Tconv; mTconv  =  memory Tconv; TransTconv  =  transitional Tconv.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111115-g002: Proportional B cell and T cell subtype changes in MS patients during fingolimod treatment.(A) CD19+ B cell subtype proportion and (B) CD4+ T cell subtype proportion within the PB of treatment-naive, IFN-β and fingolimod-treated MS patients. Results are presented as relative values within the CD19+ B cell or CD4+ T cell population. Subtype proportions were calculated as follows: (% subtype/100)×% CD19+ or CD4+ within the total lymphocyte population. Statistically significant differences compared to 0 m are shown in bold. For B cells: naive B cells; NCSM B cells  =  non class-switched memory B cells; CSM B cells  =  class-switched memory B cells and DN B cells  =  double negative B cells. For T cells: nTreg  =  naive Treg; mTreg  =  memory Treg; TransTreg  =  transitional Treg; nTconv  =  naive Tconv; mTconv  =  memory Tconv; TransTconv  =  transitional Tconv.
Mentions: Although B cell numbers were reduced in the PB after fingolimod treatment, we investigated the effects of fingolimod treatment on the remaining B cell population in the PB of treated patients. Both non class-switched (CD19+IgD+CD27+) and class-switched memory B cells (CD19+IgD-CD27+) were significantly decreased in the peripheral B cell population from 3 m until end of follow-up (p<0.001; figure 2A, table S1, figure S1). In contrast, the percentage of CD19+IgD-CD27- cells (double negative B cells) was significantly increased within the B cell population at 1 m up to 12 m (p<0.05 at 1 m; p<0.001 at 3–12 m; figure 2A, table S1, figure S1). Naive B cells (CD19+IgD+CD27-) made up about 50% of the remaining peripheral B cells and the proportion of these cells was increased after 3 m fingolimod until end of follow-up (p<0.03; figure 2A; table S1, figure 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