Immunomodulatory networks in multiple sclerosis

Background Dimethylfumarate (DMF) and ocrelizumab are two effective immunomodulators for multiple sclerosis but their mechanism of action involves different immune pathways. In this study we constructed immunomodulatory networks from cytokine and immunoprofiling data to evaluate the similarities and differences between these two disease modifying therapies in multiple sclerosis (MS). Methods Plasma and PBMCs from 16 and 13 MS patients were collected at baseline, 3 months and 6 months after treatment with DMF and ocrelizumab respectively. Cytokine analysis from plasma was performed with Olink assays and immunophenotyping was done by Cytof. Data were integrated with weighted correlation network analysis and highly interconnected modules were identified. Associations between modules and therapy was done with linear mixed effect models. Results DMF treatment was associated with a significant reduction of a module responsible for chemokine signaling pathways and cytokine-cytokine receptor interactions, whereas ocrelizumab treatment led to the increase of a module of soluble factors that are involved in tryptophan metabolism and foxp3 activation. DMF also reduced both T and B cell memory populations and ocrelizumab exerted its immunomodulatory effect by mostly reducing the frequency of memory B cells. Conclusions Our results suggest that DMF and ocrelizumab affect different immune networks to exert their effect in multiple sclerosis patients.