The interferon in idiopathic inflammatory myopathies: Different signatures and new therapeutic perspectives. A literature review

Gasparotto, Michela; Franco, Chiara; Zanatta, Elisabetta; Ghirardello, Anna; Zen, Margherita; Iaccarino, Leonardo; Fabris, B.; Doria, Andrea; Gatto, Mariele

doi:10.1016/j.autrev.2023.103334

Cited by 12 publications

(4 citation statements)

References 90 publications

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“…Specifically, these proteins have intricate associations with muscular and vascular diseases, as previously reported [60,61]. Remarkably, a causative connection was elucidated between abnormalities in transmembrane protein complexes responsible for transmembrane signal transmission and myopathy as well as other connective tissue diseases, manifesting effects on muscle structure [62][63][64].…”

Section: Discussionmentioning

confidence: 76%

Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy

Vinci,

Vitello,

Greco

et al. 2024

CIMB

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Ion channelopathies result from impaired ion channel protein function, due to mutations affecting ion transport across cell membranes. Over 40 diseases, including neuropathy, pain, migraine, epilepsy, and ataxia, are associated with ion channelopathies, impacting electrically excitable tissues and significantly affecting skeletal muscle. Gene mutations affecting transmembrane ionic flow are strongly linked to skeletal muscle disorders, particularly myopathies, disrupting muscle excitability and contraction. Electromyography (EMG) analysis performed on a patient who complained of weakness and fatigue revealed the presence of primary muscular damage, suggesting an early-stage myopathy. Whole exome sequencing (WES) did not detect potentially causative variants in known myopathy-associated genes but revealed a novel homozygous deletion of the P2RX6 gene likely disrupting protein function. The P2RX6 gene, predominantly expressed in skeletal muscle, is an ATP-gated ion channel receptor belonging to the purinergic receptors (P2RX) family. In addition, STRING pathways suggested a correlation with more proteins having a plausible role in myopathy. No previous studies have reported the implication of this gene in myopathy. Further studies are needed on patients with a defective ion channel pathway, and the use of in vitro functional assays in suppressing P2RX6 gene expression will be required to validate its functional role.

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Section: Discussionmentioning

confidence: 76%

Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy

Vinci,

Vitello,

Greco

et al. 2024

CIMB

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“…Interferon signaling is highly represented in the muscle and skin of IIM patients, together with complement cascade activation, exerting various inflammatory effects that result in muscle fibrosis ( 50 ). In particular, interferon I signaling is increased in anti-MDA5+ dermatomyositis, which greatly correlates with disease activity and can be used to predict patient mortality ( 51 , 52 ). Therefore, we hypothesized that after COVID-19 infection, myocytes respond to external stimuli to activate complement and interferon signaling via MAPK signaling, which releases large amounts of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy

Zhang,

Tao,

Cheng

et al. 2023

Front. Immunol.

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BackgroundThe coronavirus disease (COVID-19) pandemic is a serious threat to public health worldwide. Growing evidence reveals that there are certain links between COVID-19 and autoimmune diseases; in particular, COVID-19 and idiopathic inflammatory myopathies (IIM) have been observed to be clinically comorbid. Hence, this study aimed to elucidate the molecular mechanisms of COVID-19 and IIM from a genomic perspective.MethodsWe obtained transcriptome data of patients with COVID-19 and IIM separately from the GEO database and identified common differentially expressed genes (DEGs) by intersection. We then performed functional enrichment, PPI, machine learning, gene expression regulatory network, and immune infiltration analyses of co-expressed genes.ResultsA total of 91 common genes were identified between COVID-19 and IIM. Functional enrichment analysis revealed that these genes were mainly involved in immune dysregulation, response to external stimuli, and MAPK signaling pathways. The MCODE algorithm recognized two densely linked clusters in the common genes, which were related to inflammatory factors and interferon signaling. Subsequently, three key genes (CDKN1A, IFI27, and STAB1) were screened using machine learning to predict the occurrence of COVID-19 related IIM. These key genes exhibited excellent diagnostic performance in both training and validation cohorts. Moreover, we created TF-gene and miRNA-gene networks to reveal the regulation of key genes. Finally, we estimated the relationship between key genes and immune cell infiltration, of which IFI27 was positively associated with M1 macrophages.ConclusionOur work revealed common molecular mechanisms, core genes, potential targets, and therapeutic approaches for COVID-19 and IIM from a genomic perspective. This provides new ideas for the diagnosis and treatment of COVID-19 related IIM in the future.

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“…Anti-MDA5 autoantibodies are involved in the formation of immune complexes (ICs), which promote IFN production by stimulating Toll-like receptor 7 (TLR7). The interaction between anti-MDA5 autoantibodies and type I IFN creates a vicious circle [ 3 ]. In addition, type I IFN can lead to myotube mitochondrial damage by increasing reactive oxygen species production [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Explore the shared molecular mechanism between dermatomyositis and nasopharyngeal cancer by bioinformatic analysis

Zhong,

Shang,

Zhang

et al. 2024

PLoS ONE

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Background Dermatomyositis (DM) is prone to nasopharyngeal carcinoma (NPC), but the mechanism is unclear. This study aimed to explore the potential pathogenesis of DM and NPC. Methods The datasets GSE46239, GSE142807, GSE12452, and GSE53819 were downloaded from the GEO dataset. The disease co-expression module was obtained by R-package WGCNA. We built PPI networks for the key modules. ClueGO was used to analyze functional enrichment for the key modules. DEG analysis was performed with the R-package "limma". R-package “pROC” was applied to assess the diagnostic performance of hub genes. MiRNA-mRNA networks were constructed using MiRTarBase and miRWalk databases. Results The key modules that positively correlated with NPC and DM were found. Its intersecting genes were enriched in the negative regulation of viral gene replication pathway. Similarly, overlapping down-regulated DEGs in DM and NPC were also enriched in negatively regulated viral gene replication. Finally, we identified 10 hub genes that primarily regulate viral biological processes and type I interferon responses. Four key genes (GBP1, IFIH1, IFIT3, BST2) showed strong diagnostic performance, with AUC>0.8. In both DM and NPC, the expression of key genes was correlated with macrophage infiltration level. Based on hub genes’ miRNA-mRNA network, hsa-miR-146a plays a vital role in DM-associated NPC. Conclusions Our research discovered pivot genes between DM and NPC. Viral gene replication and response to type I interferon may be the crucial bridge between DM and NPC. By regulating hub genes, MiR-146a will provide new strategies for diagnosis and treatment in DM complicated by NPC patients. For individuals with persistent viral replication in DM, screening for nasopharyngeal cancer is necessary.

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The interferon in idiopathic inflammatory myopathies: Different signatures and new therapeutic perspectives. A literature review

Cited by 12 publications

References 90 publications

Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy

Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy

Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy

Explore the shared molecular mechanism between dermatomyositis and nasopharyngeal cancer by bioinformatic analysis

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