Bioinformatics analysis of gene expression profiles of Inclusion body myositis

Abstract

Inclusion body myositis (IBM) is a disease with a poor prognosis and limited treatment options. This study aimed at exploring gene expression profile alterations, investigating the underlying mechanisms and identifying novel targets for IBM. We analysed two microarray datasets (GSE39454 and GSE128470) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between IBM and normal samples. Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Finally, protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. A total of 144 upregulated DEGs and one downregulated DEG were iden-

Impaired muscle stem cell function and abnormal myogenesis in acquired myopathies

“…Specific human leukocyte antigen haplotypes are among the genetic risk factors for IIMs development [ 110 ]. Analysis of high throughput sequencing datasets has identified differentially expressed genes and dysregulated immune-related pathways that highlight the underlying mechanisms of IIMs [ 111 , 112 ]. Several proinflammatory micro-RNAs are up-regulated in IIMs and could contribute to the pathogenesis [ 113 , 114 ].…”

Idiopathic inflammatory myopathies: one year in review 2021

“…• Specific HLA haplotypes are associated with the development of IIMs in general and their subsets (3-5). Interferon regulatory factor 8 Stabilise transcription of type I IFN promoters in monocytes TYROBP (9) TYRO protein tyrosine kinase-binding protein Regulates intestinal inflammation in mice models VCAM1 (9) Vascular cell adhesion molecule I Favours muscle invasion from leukocytes HLA-DRA (9) Major histocompatibility complex, class II, DR alpha HLA class II restricted antigen presentation pathway HLA-DRB1 (9) Major histocompatibility complex, class II, DR beta 1 HLA class II restricted antigen presentation pathway HLA-DOA (10) Major histocompatibility complex, class II, DO alpha chain HLA class II restricted antigen presentation pathway, B cells antigen recognition HLA-DQA1…”

“…Major histocompatibility complex, class II, DQ alpha 1 chain HLA class II restricted antigen presentation pathway, CD4 antigen recognition CD74 (9) Major histocompatibility complex, class II invariant chain Transmembrane glycoprotein upregulated by IFN-γ CCR5 (9) C-C motif chemokine receptor 5 Membrane chemokine receptor in monocytes CXCL9 (9) C-X-C motif chemokine ligand 9 Membrane chemokine receptor in IBM muscle fibres CCL13 (10) Chemokine (C-C motif) ligand 13 Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils C1QB (9) Complement component 1, q subcomponent, B chain Possibly involved in phagocytosis of degenerating neuromuscular synapses AQP4 (9) Acquaporin-4 Water channel that is expressed in the sarcolemma of muscle fibres CD8A (10) T-cell surface glycoprotein CD8 alpha chain Coreceptor for MHC class I molecule in T cells GBP1 (10) Guanylate-binding protein 1 IFN-induced antiviral activity against influenza virus GBP5 (10) Guanylate-binding protein 5 IFN-induced NLRP3 inflammasome assembly DM XAF1 (8) X chromosome linked inhibitor of apoptosis protein related Inhibits apoptosis by binding to caspases and inhibiting the function of factor 1 caspases NT5E (8) Ecto-5́-nucleotidase membrane nuclease, marker of lymphocyte maturation, modulate lymphocyte response UGCG (8) UDP-glucose ceramide glucosyltransferase Regulates apoptosis-related pathways CMPK2 (10) mitochondrial UMP-CMP kinase 2 Involved in cell respiration TLR3 (8) Toll-like receptors 3 Recognises ds-RNA and induce NF-κB and IFN-β DDX58 (RIG-1) (8) Retinoic acid-inducible gene I Recognises viral RNA and activates innate antiviral responses (IFN I and inflammatory cytokines) STAT1 (8) Signal transducer and activator of transcription 1 Involved in many cellular process, possibly type I interferon signal transduction GBP1 (8) Guanylate binding protein 1 Early-warning signal expressed in inflammatory skin diseases PLSCR1 (8) Phospholipid scramblase 1 Can promote the apoptosis through activation of caspase 3 SP100 (8) Nuclear autoantigen Sp-100 Involved in response to viral infections and in p53 and interferon signaling IGK (8) Immunoglobulin k light chain Housekeeping gene secreted by plasmacells, possibly activating NF-κB RSAD2 (8,10) Radical S-adenosyl methionine domain-containing protein 2 Type I IFN-induced endoplasmic reticulum gene, regulates differentiation in Th2 and B cells activation ISG15 (10) Interferon-stimulated gene 15 Type I IFN-induced antiviral protein, influencing the functions of several immune cells OAS1 (10) Oligoadenylate Synthetase 1 Typ...…”

Inclusion body myositis: evolving concepts

“…Recent work showed development of greater fatty infiltration in areas of muscle with greatest STIR signal (reflective of inflammation) also lends support that inflammation drives the ''degeneration'' [9 & ]. Discovery of a potent and specific type I interferon and interferon gamma associated pathways in IBM, based on pathologic as well as transcriptomic and proteomic studies, point to a specific immuneinteraction between immune cells (particularly macrophages) and myofibers in IBM [36,[39][40][41]. Recent work has shown a strong association with three Class II MHC (HLA-DRB1) alleles, with particularly strong association with HLA-DRB1Ã03 : 01, and the risk could be largely attributed to amino acids within the peptide binding pocket [42].…”