Molecular mechanisms underlying the co-pathogenesis of abdominal aortic aneurysm and rheumatoid arthritis: evidence based on bioinformatics analysis and clinical data

BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has been reported to be associated with rheumatoid arthritis (RA). This research aimed to analyze the co-pathogenesis of AAA and RA through bioinformatics and clinical data. METHODS: Microarray and single-cell RNA sequencing (scRNA-seq) datasets for AAA and RA were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R software (v4.2.2), followed by enrichment analyses. Hub genes were identified via the STRING database and Cytoscape software (v3.10.1). An immune cell infiltration analysis was conducted to identify key immune cell types associated with AAA and RA. Hub genes and key immune cell types were further validated using scRNA-seq datasets. NetworkAnalyst and the Drug Signature Database (DSigDB) were employed to explore the associations of hub genes with related diseases, miRNAs, transcription factors (TFs), drugs, and drug targets. Additionally, peripheral blood samples from 629 clinical patients were collected to validate the results of the immune cell infiltration analysis. RESULTS: The AAA and RA dataset revealed 61 common DEGs, including 20 upregulated and 41 downregulated genes. Three hub genes were screened from the common DEGs, and ITK was validated as hub gene in both AAA and RA datasets. Immune infiltration analysis revealed significant upregulation of monocytes in both AAA and RA, positively correlated with ITK expression. This was validated by scRNA-seq datasets confirming elevated ITK levels in monocytes. A total of eighteen related diseases, ten target miRNAs, eight TFs, and the top ten drugs and drug targets associated with ITK were identified. Analysis of clinical data revealed that monocyte levels were significantly elevated in patients with AAA and RA. CONCLUSIONS: Our study suggests that ITK may serve as a potential biomarker involved in the co-pathogenesis of AAA and RA. Moreover, monocytes appear to play an important role in this process. The regulatory network constructed for ITK may offer preliminary insights for future research.