Integrated proteomic and transcriptomic profiles reveals the role of OAS3 in dermatomyositis pathogenesis.

BACKGROUND

Dermatomyositis (DM) is an autoimmune myopathy often linked to aberrant type I interferon (IFN) pathway activation. However, the molecular mediators driving this IFN signature and their utility as biomarkers remain incompletely defined.

METHODS

We conducted an integrated multi-omics analysis combining plasma proteomics from 14 patients with DM and 5 healthy controls, with transcriptomic profiling of skeletal muscle derived from three publicly available Gene Expression Omnibus datasets (GSE11971, GSE1551, and GSE128470). Selected plasma proteins were further quantified and validated using enzyme-linked immunosorbent assay (ELISA).

RESULTS

Proteomic profiling identified 482 differentially expressed proteins (DEPs). Upregulated DEPs were enriched in antiviral responses and IFN-related immune pathways, while downregulated DEPs were associated with extracellular matrix organization. Transcriptomic analysis revealed 156 consistently upregulated differentially expressed genes across datasets, primarily involved in innate immunity, nucleic acid sensing, and antigen presentation. Integrative analysis identified 2'-5'-oligoadenylate synthetase 3 (OAS3) as a central hub within the IFN signaling network. ELISA validation demonstrated significantly elevated plasma OAS3 levels in DM patients (median: 5.073 ng/ml, IQR: 2.93-9.36) compared with controls (median: 2.723 ng/mL, IQR: 1.77-3.34), with a P-value of 0.018. Notably, plasma OAS3 levels showed a positive correlation with serum creatine kinase concentrations (r=0.55, P = 0.044).

CONCLUSIONS

OAS3 expression was consistently elevated in both plasma and skeletal muscle tissues of individuals with DM. This molecule may act as a key enhancer of type I IFN-mediated pathogenic responses. Our results support the potential of OAS3 as a novel biomarker and therapeutic target in DM.