Genome-wide analysis of abnormal splicing regulators and alternative splicing involved in immune regulation in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex clinical manifestations and no current cure. Alternative splicing (AS) plays a key role in SLE by regulating immune-related genes, but its genome-wide regulatory mechanisms remain unclear. To investigate the involvement of abnormal splicing regulators and AS events in the immune regulation of SLE. Transcriptome data from the SLE dataset GSE162828 were analyzed for differential gene expression and AS events using bioinformatics tools. Immune infiltration analysis was conducted with CIBERSORT, and co-expression of key splicing factors (SFs) and AS events was assessed using SUVA software. A total of 5144 differentially expressed genes and 73 SFs were identified. Significant immune cell differences were observed between SLE and controls, highlighting SFs such as HNRNPDL, RBM47, TIA1, SSB, and DHX15. Eighty-three AS events were identified, with IRF9 and PTPRC emerging as key regulatory events linked to SLE. Dysregulated SFs influence AS in immune-related genes, affecting immune cell composition and SLE progression. These findings offer potential new therapeutic targets for modulating the immune microenvironment in SLE.