IFN-beta and EIF2AK2 are potential biomarkers for interstitial lung disease in anti-MDA5 positive dermatomyositis

Abstract

Objective: DM with positive anti-melanoma differentiation-related gene 5 (MDA5) antibody is an autoimmune disease with multiple complications. Interstitial lung diseases (ILDs) are significantly associated with DM and are particularly related to MDA5+ DM. This article aims to explore potential molecular mechanisms and develop new diagnostic biomarkers for MDA5+ DM-ILD.

Methods: The series matrix files of DM and non-specific interstitial pneumonia (NSIP) were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) was used to screen the common enriched pathways related to DM and NSIP. Next, the co-expressed differential expressed genes (co-DEGs) between MDA5+, MDA5- and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein-protein interaction (PPI) network construction. The mRNA expression levels of IFN-beta and EIF2AK2 were measured by RT-qPCR. The protein expression levels of IFN-beta were measured by ELISA.

Results: Using GSEA, the enriched pathway 'herpes simplex virus 1 infection' was both up-regulated in DM and NSIP. Enrichment analysis in MDA5+ DM, MDA5- DM and NSIP reported that the IFN-beta signalling pathway was an important influencing factor in the MDA5+ DM-ILD. We also identified that eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) was an important gene signature in the MDA5+ DM-ILD by PPI analysis. The expression levels of IFN-beta and EIF2AK2 were significantly increased in MDA5+ DM-ILD patients.

Conclusions: IFN-beta and EIF2AK2 contributed to the pathogenesis of MDA5+ DM-ILD, which could be used as potential therapeutic targets.

Keywords: MDA5; dermatomyositis; differentially expressed genes; functional enrichment analysis; interstitial lung disease.