Immune-related genes probably increase the occurrence of Interstitial Lung Disease in Dermatomyositis

Abstract

Abstract Background Interstitial lung disease (ILD) is one of the significant complications of dermatomyositis (DM), but the mechanisms by which it occurs remain incompletely elucidated. This study aimed to explore further the possible genetic mechanisms by which this complication occurs. Methods Gene expression profiles for dermatomyositis (GSE39454, GSE46239, GSE143323) and interstitial lung disease (GSE32537, GSE110147, GSE150910) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying common differentially expressed genes (DEGs) to dermatomyositisand interstitial lung disease using the "limma" R package and the "VennDiagram" R package, functional annotation, relationship to immune cell infiltration, identification of transcription factors (TFs). We also collected clinical cases of dermatomyositis-associated interstitial lung disease (DM-ILD), including 3 cases of rapidly progressive interstitial lung diseases and 3 cases of none-rapidly progressive interstitial lung diseases, and explored whether there were differences in serum lymphocyte subpopulations. Results A total of 4 common DEGs (SLAMF7, SPP1, TDO2, and VCAM1) were screened and GO enrichment analysis showed that these genes were mainly enriched in T cell activation, regulation of lymphocyte activation, lymphocyte differentiation, leukocyte proliferation and regulation of T cell activation. In terms of KEGG pathways, the three significantly enriched pathways were the PI3K-Akt signaling pathway, MAPK signaling pathway, and Cytokine-cytokine receptor interaction. In lung and muscle tissues, 21 and 3 TFs may regulate the expression of these genes, respectively. Finally, by analysing the serum lymphocyte subpopulations, we also found a decrease in the absolute number of CD8+ T cells and an increase in the CD4+ /CD8+ T cell ratio in dermatomyositis combined with rapidly progressive interstitial lung disease. Conclusion These common pathways and key genes may provide new ideas for further research into DM-ILD.