Unraveling the Molecular Mechanisms of cSLE Through Integrated Serum Metabolomics, Network Pharmacology, and Molecular Docking Approaches.

Abstract

Childhood-onset systemic lupus erythematosus (cSLE) is recognized as a chronic, systemic autoimmune disorder that manifests during childhood. Compared to adult-onset SLE, cSLE is characterized by higher disease activity and greater cumulative organ damage, thereby requiring more intensive immunosuppressive therapy. Although early diagnosis remains challenging, it is considered essential for improving clinical outcomes. In the present study, the serum metabolomic profiles of 100 cSLE patients and 40 healthy controls were comprehensively analyzed. Through the integration of differentially expressed metabolites, nine key metabolites were identified that effectively distinguished cSLE patients from healthy individuals. Moreover, unsaturated fatty acids were found to potentially modulate the JAK2/STAT3 signaling pathway, suggesting a role in disease progression. Overall, these findings underscore the potential value of investigating unsaturated fatty acids to gain mechanistic insight into cSLE pathogenesis and to uncover novel therapeutic targets.