GEO Data Sets Analysis On Mechanism of Action of IFNβ-1a Treatment in Multiple Sclerosis

Abstract

Multiple Sclerosis (MS) is an autoimmune disease that affects millions of people worldwide and causes symptoms such as dysarthria, ataxia, and nystagmus. MS is known to be characterized by an autoimmune attack by the immune system on the myelin sheath of neurons, causing inflammation and scarring (sclerosis). In the status quo, MS is treated or alleviated by disease-modifying therapies, including beta interferons (IFNβ) and monoclonal antibodies. Yet, the mechanism of action (MOA) of IFNβ is not fully understood, and only a limited proportion of patients respond to IFNβ treatment. Mononuclear cells from therapy-naïve MS patients, IFN-β-1a-treated MS patients after 12 months from three databases on GEO are analysed to examine RNA changes that characterize both the disease and its treatment. 28 differentially expressed genes (DEGs) are identified in all three of the databases and passed the cut-off criteria. Using the 28 DEGs, we performed DAVID and PANTHER analysis, revealing that the biological process “immune response”, “defence against virus”, and “regulation of viral genome replication” are enriched. A protein interaction network for the DEGs was constructed and a protein module was identified and analysed with PANTHER, revealing “interleukin-27-mediated signalling pathway”, “regulation of ribonuclease activity”, “regulation of type III interferon production”, “cellular response to exogenous double-stranded RNA (dsRNA)”, and “ISG15-protein conjugation are enriched for > 100 folds. Cytoscape analysis further identified the hub genes IFI44L, IFI44, PLSCR1, and STAT1 and they may be important mediators in the therapeutic effect of IFNβ treatment and warrant further study. Overall, the findings of the present study provide insights into the MOA of IFNβ-1a and provide greater confidence on which genes are differentially expressed in MS before and after IFNβ-1a treatment. The results also are additional evidence for the role of viral infection in MS, a topic that is gaining interest in the MS research community.