Contributions
Abstract: P969
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a haematopoietic growth factor and an inflammatory cytokine produced by T cells and other immune cells. Recent evidence suggests that GM-CSF has an important role in MS pathogenesis. Our aim was to evaluate the expression of GM-CSF by different subtypes of peripheral blood mononuclear cells (PBMC) in MS patients and controls, and to determine the key factors regulating its expression.
Patients and methods: All patients were untreated RRMS. PBMCs were isolated and stimulated with anti-CD3+anti-CD28 for 5 days. Natural killer (NK) cells were isolated and cultured with different stimuli for 3 days. Cytokines from cell culture supernatants of stimulated PBMCs were measured with multiplex assay. Cells were phenotyped for lineage and intracellular cytokines, including GM-CSF, using flow cytometry.
Results: GM-CSF is expressed at significantly higher frequency by stimulated helper T (Th), cytotoxic T (Tc), and NK cells in untreated RRMS patients than healthy volunteers. There was a statistically significant increase in overall interferon-gamma (IFN-G) production in MS compared to healthy controls (MS n=10, controls n=10). Isolated and stimulated NK cells did not have different GM-CSF expression in MS patients and controls (MS n=7, controls n=5). Culture supernatants were shown to have significantly higher IL-2 and IL-12 in MS patients than controls (MS n=14, controls n=10), and blocking IL-2 significantly reduced GM-CSF expression.
Conclusion: Th (Th1 and Th17), NK, and Tc cells are all high producers of GM-CSF in MS, GM-CSF expression is reduced by blocking IL-2. The recent safety and tolerability results of a phase I trial of a monoclonal antibody in MS are encouraging. Therefore, GM-CSF is a potential therapeutic target in MS.
Disclosure: Jehan Aram: Nothing to disclose
Bruno Gran: Nothing to disclose
CS Constantinescu has received research support, travel support for meetings and consultancy fees from Biogen, Bayer, Genzyme, Merck, Morphosys, Novartis, Roche, Sanofi-Pasteur MSD and Teva. this study is supported, in part, by the Forman Hardy Foundation via the University of Nottingham.
Abstract: P969
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Background: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a haematopoietic growth factor and an inflammatory cytokine produced by T cells and other immune cells. Recent evidence suggests that GM-CSF has an important role in MS pathogenesis. Our aim was to evaluate the expression of GM-CSF by different subtypes of peripheral blood mononuclear cells (PBMC) in MS patients and controls, and to determine the key factors regulating its expression.
Patients and methods: All patients were untreated RRMS. PBMCs were isolated and stimulated with anti-CD3+anti-CD28 for 5 days. Natural killer (NK) cells were isolated and cultured with different stimuli for 3 days. Cytokines from cell culture supernatants of stimulated PBMCs were measured with multiplex assay. Cells were phenotyped for lineage and intracellular cytokines, including GM-CSF, using flow cytometry.
Results: GM-CSF is expressed at significantly higher frequency by stimulated helper T (Th), cytotoxic T (Tc), and NK cells in untreated RRMS patients than healthy volunteers. There was a statistically significant increase in overall interferon-gamma (IFN-G) production in MS compared to healthy controls (MS n=10, controls n=10). Isolated and stimulated NK cells did not have different GM-CSF expression in MS patients and controls (MS n=7, controls n=5). Culture supernatants were shown to have significantly higher IL-2 and IL-12 in MS patients than controls (MS n=14, controls n=10), and blocking IL-2 significantly reduced GM-CSF expression.
Conclusion: Th (Th1 and Th17), NK, and Tc cells are all high producers of GM-CSF in MS, GM-CSF expression is reduced by blocking IL-2. The recent safety and tolerability results of a phase I trial of a monoclonal antibody in MS are encouraging. Therefore, GM-CSF is a potential therapeutic target in MS.
Disclosure: Jehan Aram: Nothing to disclose
Bruno Gran: Nothing to disclose
CS Constantinescu has received research support, travel support for meetings and consultancy fees from Biogen, Bayer, Genzyme, Merck, Morphosys, Novartis, Roche, Sanofi-Pasteur MSD and Teva. this study is supported, in part, by the Forman Hardy Foundation via the University of Nottingham.