Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature
Authors' conclusion
This study highlights mitochondrial dysfunction as a consistent pathological feature in JDM muscle, which may be independent of interferon-driven inflammation.
Study context
- Population
- Muscle biopsies from patients with treatment-naive juvenile dermatomyositis (JDM) and age-matched controls; validation in 19 JDM cases and a bulk RNAseq dataset of 4 JDM cases
- Participants
- 3 vs 3
- Comparison
- Treatment-naive JDM muscle vs healthy paediatric muscle
- JDMn = 3
- Controlsn = 3reference
Methodological detailsspatial transcriptomics (Nanostring GeoMx Digital Spatial Profiler), age-matched controls, validation by immunohistochemistry, chemical stains and bulk RNAseq
- Spatial transcriptomics (Nanostring GeoMx Digital Spatial Profiler)
- Age-matched controls
- Validation by immunohistochemistry, chemical stains and bulk RNAseq
Main finding
As reported in the abstract
- Significant interferon pathway activation and mitochondrial dysfunction in JDM muscle vs controls
- 15-gene interferon signature significantly elevated in JDM muscle and macrophage-enriched regions, correlating with clinical weakness
- Mitochondrial dysregulation (downregulated respiratory chain pathways) present regardless of interferon activity or muscle strength
- Interferon-driven and mitochondrial signatures replicated in independent RNAseq dataset; lack of association between interferon signature and mitochondrial dysregulation validated in 19 cases by conventional staining
- Distinct transcriptomic profiles between JDM and controls, and between JDM patients with varying clinical phenotypes
Original publication
Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature. Ann Rheum Dis. Published 9 August 2025. doi:10.
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