Abstract
Introduction: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder with heterogeneous clinical manifestations and limited specific biomarkers. Advances in transcriptomic profiling offer an opportunity to dissect underlying molecular mechanisms and identify therapeutic targets.
Objectives: To perform a comprehensive bioinformatics analysis of gene expression profiles in peripheral blood of SLE patients and to identify differentially expressed genes (DEGs), functional pathways, key regulatory genes (hub genes), and druggable targets.
Materials and Methods: This is an in-silico study based on gene expression data (GSE17755) from 10 SLE patients and 20 healthy controls were analyzed using GEO2R. DEGs were subjected to functional enrichment analysis [Gene ontology (GO) and Reactome], protein-protein interaction (PPI) network construction (STRING, Cytoscape), hub gene identification (CytoHubba), cluster detection (ClusterONE), and drug-target interaction mapping (DrugBank).
Results: A total of 1,450 DEGs were identified between SLE patients and healthy controls. Gene ontology and Reactome analyses highlighted enrichment in innate immune responses, interferon signaling, and cytokine-mediated pathways. Thirteen key hub genes including GAPDH, PTEN, PTPRC, UBA52, and ISG15 were identified across multiple centrality metrics. ClusterONE detected significant modules enriched in immune-related genes, ribosomal proteins, keratin family genes, and transcription factors. Drug-target analysis revealed GAPDH as the most connected node, interacting with compounds like artenimol, omigapil, and xanthinol, indicating potential avenues for drug repurposing.
Conclusion: Our integrative analysis highlighted interferon signaling, cytokine-mediated pathways, and innate immune responses as central mechanisms in SLE. Drug–target mapping suggested several compounds, including artenimol, omigapil, NADH, 4-(2-aminoethyl) benzenesulfonyl fluoride, xanthinol, copper, and phosphatidylethanolamine, as potential modulators of key hub genes. These findings provide preliminary hypotheses that may guide future research; however, additional validation in molecular (in-vitro) experiments and animal (in-vivo) models is required before any translational application can be considered.