Contributions
Abstract: P1169
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Dimethyl fumarate (DMF) is an oral first-line therapy for relapsing remitting multiple sclerosis (RRMS). Although beneficial clinical effects have been demonstrated, the exact effects of DMF on the immune system are not completely elucidated. The aim of this study was to analyse the direct and indirect effects of DMF on the distribution and function of peripheral immune cells in RRMS patients.
In a follow-up study, peripheral blood was collected from 12 RRMS patients before, after 3 months and after 1 year of DMF treatment. Numbers of immune cells, distribution of T and B cell subtypes and
T helper cell cytokine expression, including IFN-y, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-17, IL-4 and IL-10, were determined by flow cytometry. Similar analyses were performed in a cross-sectional study of 25 untreated and 60 DMF treated RRMS patients to include more time points of DMF treatment. In vitro addition of DMF to B cell cultures was used to analyse direct effects on B cell apoptosis (annexin V) and expression of costimulatory molecules (CD40, CD80, CD86), antigen presentation major histocompatibility complex (MHC)II molecules and B cell activating factor receptor (BAFFR).
After 12 months of DMF treatment, an increase in monocyte and natural killer cell frequencies was detected while no effect was observed on total T and B cell frequencies. Nonetheless, a decrease in pro-inflammatory T cell subsets, including memory and effector memory CD4+ and CD8+ T cells, was evident while naive CD4+ and CD8+ T cells increased. A decreased percentage of IFN-y, GM-CSF and IL-17 positive T helper cells was detected. In the B cell population, double negative, class-switched and non class-switched memory B cell frequencies were decreased, while transitional and naïve B cells were increased. In the cross-sectional study, DMF induced changes in the distribution of T cell subsets after 3 months although not yet significant and was fully effective after 6 months of therapy. In vitro experiments demonstrated DMF induced apoptosis of B cells in a direct and concentration dependent manner. Further, DMF decreased expression of the costimulatory molecule CD40, MHCII and the survival marker BAFFR on B cells.
Longitudinal results indicated a redistribution of T and B cell subtypes in DMF-treated RRMS patients. DMF induced apoptosis of B cells and decreased the expression of functional B cell markers, thereby influencing B cell function.
Disclosure:
G. Montes Diaz: received research grant from Biogen
J. Fraussen: nothing to disclose
B. Van Wijmeersch: received Research and Travel Grants, Honoraria for MS-Expert Advise and Speakers Fees from:Bayer-Schering, Biogen, Sanofi Genzyme, Merck-Serono, Novartis, Roche and TEVA
R. Hupperts: received research grants and honoraria for advisory boards from: BIOGEN,Merck and Sanofi-Genzyme.
V. Somers: received research grant from Biogen
Abstract: P1169
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Dimethyl fumarate (DMF) is an oral first-line therapy for relapsing remitting multiple sclerosis (RRMS). Although beneficial clinical effects have been demonstrated, the exact effects of DMF on the immune system are not completely elucidated. The aim of this study was to analyse the direct and indirect effects of DMF on the distribution and function of peripheral immune cells in RRMS patients.
In a follow-up study, peripheral blood was collected from 12 RRMS patients before, after 3 months and after 1 year of DMF treatment. Numbers of immune cells, distribution of T and B cell subtypes and
T helper cell cytokine expression, including IFN-y, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-17, IL-4 and IL-10, were determined by flow cytometry. Similar analyses were performed in a cross-sectional study of 25 untreated and 60 DMF treated RRMS patients to include more time points of DMF treatment. In vitro addition of DMF to B cell cultures was used to analyse direct effects on B cell apoptosis (annexin V) and expression of costimulatory molecules (CD40, CD80, CD86), antigen presentation major histocompatibility complex (MHC)II molecules and B cell activating factor receptor (BAFFR).
After 12 months of DMF treatment, an increase in monocyte and natural killer cell frequencies was detected while no effect was observed on total T and B cell frequencies. Nonetheless, a decrease in pro-inflammatory T cell subsets, including memory and effector memory CD4+ and CD8+ T cells, was evident while naive CD4+ and CD8+ T cells increased. A decreased percentage of IFN-y, GM-CSF and IL-17 positive T helper cells was detected. In the B cell population, double negative, class-switched and non class-switched memory B cell frequencies were decreased, while transitional and naïve B cells were increased. In the cross-sectional study, DMF induced changes in the distribution of T cell subsets after 3 months although not yet significant and was fully effective after 6 months of therapy. In vitro experiments demonstrated DMF induced apoptosis of B cells in a direct and concentration dependent manner. Further, DMF decreased expression of the costimulatory molecule CD40, MHCII and the survival marker BAFFR on B cells.
Longitudinal results indicated a redistribution of T and B cell subtypes in DMF-treated RRMS patients. DMF induced apoptosis of B cells and decreased the expression of functional B cell markers, thereby influencing B cell function.
Disclosure:
G. Montes Diaz: received research grant from Biogen
J. Fraussen: nothing to disclose
B. Van Wijmeersch: received Research and Travel Grants, Honoraria for MS-Expert Advise and Speakers Fees from:Bayer-Schering, Biogen, Sanofi Genzyme, Merck-Serono, Novartis, Roche and TEVA
R. Hupperts: received research grants and honoraria for advisory boards from: BIOGEN,Merck and Sanofi-Genzyme.
V. Somers: received research grant from Biogen