To perform a bioinformatics-based analysis of gene enrichment and immune cell infiltration according to the gene expression profile data of IgA nephropathy (IgAN), aiming to study the IgAN-related immune mechanisms.

We obtained the GSE93798 bulk RNA-seq data of IgAN kidney tissues from the Gene Expression Omnibus (GEO) database, and the limma software package was used to screen the differentially expressed genes between normal control and IgAN. The ggplot2 software package was applied for pathway enrichment analysis through the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. The CIBERSORT software was applied to obtain the immune cells infiltration matrix, and the single cell RNA sequence data of IgAN kidney tissues were obtained from the GSE127136 chip of the GEO database. The principal component analysis (PCA) and the t-distributed stochastic neighbour embedding (t-SNE) methods were used to obtain subpopulations of cells and their marker genes, and GO and KEGG analyses were performed for the marker genes of the immune cells.

Compared with the normal control group, the IgAN kidney tissue group showed that the expression of 243 genes was significantly up-regulated, while the expression of 104 genes significantly down-regulated. The GO analysis indicated that the differentially-expressed genes in IgAN were mostly related to immune biological processes, and the KEGG pathway analysis suggested that the differentially-expressed genes in IgAN were mostly enriched in infection and immune pathways. The immune cells infiltration analysis showed that naive B cells and neutrophils were down-regulated while the plasma cells and M2 macrophages were up-regulated in the IgAN kidney tissues. Single-cell sequencing analysis results suggested that CD8⁺ T cells were mainly involved in metabolism-related processes, and M2 macrophages mainly involved in both immune- and metabolism-related processes.

The immune played an important role in the occurrence and development of IgAN. CD8⁺ T cells and M2 macrophages were involved in the pathophysiological mechanism, and may serve as the targets for the intervention of IgAN.