A Systems Medicine Approach Reveals Disordered Immune System and Lipid Metabolism in Multiple Sclerosis Patients

Summary

Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein datasets visualized using Gephi, based on protein-protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ABCC1, NOTCH1, MET, RAF1, and VAV1 was found in NDP and was involved in overrepresented terms correlated with cell-mediated immunity and cancer. In contrast, RELB, EP300, ACACB, ADIPOQ, and PCK2 had major contributions to viral infections and lipid metabolism, as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity. This article is protected by copyright. All rights reserved.