Integrated multi-omics analysis reveals diagnostic biomarkers and therapeutic targets for systemic lupus...

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with poorly understood molecular mechanisms. This study investigated causal relationships between plasma proteins and SLE using two-sample Mendelian randomization analysis based on genome-wide association study data. Functional enrichment analyses Gene Ontology and Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network analysis identified apolipoprotein A2, MANSC domain-containing protein 1, and proteasome subunit beta 5 as key genes involved in glycoprotein metabolism and immune responses. Molecular docking simulations suggested meglumine and vorinostat as potential therapeutic candidates. A diagnostic nomogram model incorporating these genes demonstrated high predictive accuracy (area under the curve = 0.968). Single-cell RNA sequencing revealed that proteasome subunit beta 5 and MANSC domain-containing protein 1 were predominantly expressed in T cells and monocytes, implicating their roles in SLE-associated immune dysregulation. These findings highlight novel biomarkers, diagnostic tools, and therapeutic targets for SLE, advancing our understanding of its pathogenesis and treatment.