A systems biology approach to identify common molecular signatures in Hashimoto's thyroiditis and rheumatoid...

Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) are prevalent autoimmune disorders with substantial clinical overlap, yet the shared molecular mechanisms underlying their comorbidity remain poorly understood.

Publicly available GEO datasets were analyzed to identify differentially expressed genes (DEGs) and hub genes. Functional enrichment analysis was performed to characterize biological processes associated with these DEGs. Single-sample gene set enrichment analysis (ssGSEA) was applied to assess immune cell infiltration patterns. A transcription factor‑mRNA‑microRNA (TF-mRNA-miRNA) regulatory network was constructed to pinpoint key regulators, and drug target prediction was conducted via the QuartataWeb platform.

Bioinformatics analysis of the GEO dataset identified 196 DEGs, including 10 hub genes. Enrichment analyses linked the DEGs to pathways involved in inflammation and immune regulation. ssGSEA revealed that activated B cells play a central role in disease pathogenesis. The regulatory network identified multiple critical modulators, and drug target analysis computationally predicted CD2, CTLA4, and CD27 as potential therapeutic targets.

Our study findings suggest that the disruption of immune tolerance and aberrant immune activation are likely the primary mechanisms driving the comorbidity of HT and RA. The identified hub genes and their potential druggable targets provide a theoretical basis for subsequent experimental validation and the development of precision therapeutic strategies.