Plasma proteomics (>1,000 proteins via Olink Proximity Extension Assay) was used to profile tissue-specific and immune biomarkers in 201 patients with IIM subtypes — dermatomyositis, anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis — at Karolinska University Hospital.
Each IIM subtype showed a distinct plasma protein signature: dermatomyositis enriched for IFN signaling and skin-associated proteins, ASyS for lung-associated proteins, IMNM for muscle-associated proteins (highest skeletal muscle tissue score), and inclusion body myositis for T-cell response proteins. Skeletal muscle scores correlated strongly with muscle disease activity VAS, creatine kinase levels, and muscle weakness scores; surfactant proteins and IFN pathway activation were enriched in ILD patients with anti-MDA5 and anti-Jo1 autoantibodies.
Single-center cohort (Karolinska University Hospital) limits generalizability. Cross-sectional design prevents causal inference about protein changes over disease course. The study does not report longitudinal or treatment-response data.
Plasma proteomic tissue scores — especially skeletal muscle scores for IMNM and lung scores for ASyS — track closely with established disease activity measures, suggesting future utility as non-invasive biomarkers. Clinicians should be aware that IFN pathway activation and surfactant protein enrichment may help distinguish ILD subsets driven by anti-MDA5 vs. anti-Jo1 autoantibodies.
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