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



Pazhouhandeh M¹ ; Sahraian MA² ; Siadat SD^{1, 3} ; Fateh A^{1, 3} ; Vaziri F^{1, 3} ; Tabrizi F¹ ; Ajorloo F^{1, 4} ; Arshadi AK¹ ; Fatemi E⁵ ; Piri Gavgani S¹ ; Mahboudi F⁵ ; Rahimi Jamnani F^{1, 3} Show Affiliations
Source: Clinical and Experimental Immunology Published:2018

Abstract

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 data sets 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 ATP binding cassette subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1 (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in NDP and was involved in over-represented terms correlated with cell-mediated immunity and cancer. In contrast, transcription factor RelB (RELB), histone acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (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. © 2017 British Society for Immunology