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

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 clinical...

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Main Authors: Zhao Zhang, Weidong Tao, Debin Cheng, Marong Qin, Jun Fu, Dong Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197493/full
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author Zhao Zhang
Weidong Tao
Debin Cheng
Marong Qin
Jun Fu
Dong Liu
author_facet Zhao Zhang
Weidong Tao
Debin Cheng
Marong Qin
Jun Fu
Dong Liu
author_sort Zhao Zhang
collection DOAJ
description 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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spelling doaj.art-1de65786521248418ebeae226561bdbe2023-08-10T21:42:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.11974931197493Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathyZhao Zhang0Weidong Tao1Debin Cheng2Marong Qin3Jun Fu4Dong Liu5Department of Orthopaedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, ChinaDepartment of Orthopaedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, ChinaDepartment of Orthopaedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, ChinaSchool of Chemistry, Cardiff University, Cardiff, United KingdomDepartment of Orthopaedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, ChinaDepartment of Orthopaedics, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, ChinaBackgroundThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197493/fullCOVID-19idiopathic inflammatory myopathiesmolecular mechanismsimmune dysregulationbiomarker
spellingShingle Zhao Zhang
Weidong Tao
Debin Cheng
Marong Qin
Jun Fu
Dong Liu
Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
Frontiers in Immunology
COVID-19
idiopathic inflammatory myopathies
molecular mechanisms
immune dysregulation
biomarker
title Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
title_full Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
title_fullStr Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
title_full_unstemmed Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
title_short Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
title_sort deciphering the crosstalk of immune dysregulation between covid 19 and idiopathic inflammatory myopathy
topic COVID-19
idiopathic inflammatory myopathies
molecular mechanisms
immune dysregulation
biomarker
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197493/full
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