Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) share immune dysregulation but diverge biologically and clinically. SSc features fibrosis and vascular dysfunction of skin/connective tissue, while SLE is driven by autoantibodies, immune complex deposition, and multi-organ inflammation. In a transcriptomic study of patients who were immunosuppressant-free (SSc n=10; SLE n=24) vs controls, investigators identified 3,895 differentially expressed genes in SLE and 2,055 in SSc. Regulator of G-protein signaling 5—a mediator of vascular homeostasis and pericyte function—was significantly downregulated in both diseases (more so in SSc), nominating it as a shared biomarker and potential therapeutic target.
Disease-specific signals also emerged. EGR1 (linked to fibrotic remodeling) was upregulated in SSc, while BLK, ITGAM, and IFNG (implicated in B-cell signaling and immune activation) were upregulated in SLE, suggesting avenues for antifibrotic (EGR1-directed) and B-cell–targeted (eg, BLK-directed) strategies. The authors emphasize this is an early, small-cohort analysis. Larger, well-phenotyped cohorts and functional studies are needed to validate targets, define pathways, and translate findings into biomarkers and precision therapies. Even so, the work illustrates how transcriptome profiling can parse overlap vs divergence between SSc and SLE and guide more tailored diagnostics and treatments.
Reference: Kaltwasser J. Study Identifies SSc, SLE Gene Expression Signatures. AJMC. Published August 14, 2025. Accessed October 2, 2025. https://www.ajmc.com/view/study-identifies-ssc-sle-gene-expression-signatures
Link: https://www.ajmc.com/view/study-identifies-ssc-sle-gene-expression-signatures
