A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

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 r...

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Bibliographic Details
Published in:Clinical and experimental immunology Vol. 192; no. 1; pp. 18 - 32
Main Authors: Pazhouhandeh, M., Sahraian, M.‐A., Siadat, S. D., Fateh, A., Vaziri, F., Tabrizi, F., Ajorloo, F., Arshadi, A. K., Fatemi, E., Piri Gavgani, S., Mahboudi, F., Rahimi Jamnani, F.
Format: Journal Article
Language:English
Published: England Oxford University Press 01-04-2018
John Wiley and Sons Inc
Subjects:
Adiponectin
Autoantibodies
Autoantigens
c-Met protein
Cancer
Chemical compounds
disease‐modifying therapies
Drug development
Event-related potentials
Hepatocyte growth factor
Histone acetyltransferase
Homology
Immune system
Immunosuppressive agents
Kinases
Lipid metabolism
Metabolism
Mitochondria
Multiple sclerosis
Notch1 protein
Original
Pathogenesis
Peptides
Phages
Protein interaction
Protein kinase
Proteins
Raf protein
relapsing–remitting multiple sclerosis
RelB protein
Sclerosis
Side effects
systems medicine approach
therapeutic targets
Threonine
disease-modifying therapies
therapeutic targets
autoantibodies
relapsing-remitting multiple sclerosis
systems medicine approach
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Summary: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 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. A systems medicine approach reveals events related to the development of multiple sclerosis (MS). Cell‐mediated immunity and cancer are overrepresented terms in MS patients before treatment. Therapies targeting disordered lipid metabolism may help to ameliorate MS.
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ISSN:0009-9104
1365-2249
DOI:10.1111/cei.13087