Exploration of Common Genomic Signatures of Systemic Juvenile Rheumatoid Arthritis and Type 1 Diabetes

Abstract

Abstract Objective To explore the genetic characteristics of systemic juvenile rheumatoid arthritis (sJIA) and type 1 diabetes mellitus (T1D). Methods The microarray data of sJIA and T1D from Gene Expression Omnibus (GEO) were analyzed. The shared differentially expressed genes (SDEGs) were identified by the GEO2R tool, and genes of extracellular proteins were identified. Then, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (IRGs) that are associated with pJIA and T1D. In addition, transcription factors (TFs) and their target genes in SDEGs were obtained by comparing databases from HumanTFDB, ENCODE, JASPAR, and TRRUST. Finally, functional enrichment analyses of the previously identified gene sets were performed by g: Profiler. Results We found 285 up-regulated and 97 down-regulated SDEGs via GEO2R, and by constructing a TFs-targeted SDEGs network, 5 key TFs (KLF9, ARID3A, ZNF639, NEF2, MYB) were screened. Functional enrichment analyses of SDEGs, IRGs, and TFs-targeted SDEGs suggested the important role of the innate immune system, JAK-STAT and Ras-MAPK-ERK signaling pathways in the pathogenesis of sJIA and T1D, involving biological processes such as neutrophils and mononuclear cells, phosphorylation, transcellular signaling, and transferase activity, etc. Conclusion Innate immune abnormalities play important roles in sJIA and T1D, and the JAK-STAT and Ras-MAPK-ERK pathways, which are closely related to inflammation and immune regulation, may be involved. The regulatory roles of KLF9, ARID3A, ZNF639, NEF2, and MYB in this network need to be further investigated.