An integrative bioinformatics investigation and experimental validation of immune- related genes in overflow arteriovenous fistula

Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, the low rate of AVF maturation is a pressing issue. While the role of immunity and inflammation in AVF has been recognized, there is no research describing their effects on AVF maturation from a bioinformatics perspective. In this study, we analyzed the GSE119296 dataset to identify differentially expressed genes (DEGs) and then performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) and Gene Set Enrichment Analysis (GSEA). We also performed immune cell infiltration analysis and identified differentially expressed immune-related genes (DEIRGs). Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We found that the proportion of macrophages, plasma cells and follicular helper T cells increased significantly in matured AVF. The gene expression of candidate hub genes obtained from the PPI network increased sequentially in native veins, failed AVFs, and matured AVFs. We validated the candidate hub genes using qRT-PCR and immunohistochemistry, and ultimately identified three hub genes (IL1B, IL6, CXCR4). Our bioinformatics research provides potential targets to further explore the effects of inflammation and immunity in AVF.