Identification of eight pathological signatures that are overrepresented in an inflammatory myopathy

Immune-mediated necrotising myopathies (IMNM) are inflammatory myopathies characterised by necrosis of muscle fibres, complement deposits around non-necrotic fibres, and macrophage infiltrates. Patients with this condition present with muscle lesions accompanied by fibro-adipose replacement, which leads to inadequate recovery of muscle strength; however, the pathogenic mechanism underlying these diseases remains poorly understood.

Researchers at the Institute have investigated the pathogenesis of IMNMs using a spatial transcriptomics technique on muscle biopsies from patients with myositis. This approach enabled the analysis of the expression of several relevant genes, taking into account their spatial localisation within the muscle.

The authors thus identified specific inflammatory signatures for IMNM – fibrotic, regenerative and related to lipid metabolism. These differ from those observed in other forms of myositis and exhibit a specific distribution within necrotic and perinecrotic areas. Indeed, the necrotic muscle areas in IMNM are associated with a specific subtype of fibroblasts expressing SFRP4, which interacts with macrophages. This interaction may underlie the pathological muscle phenotype and contribute to the inflammationRéaction non spécifique suscitée par un agent pathogène., fibro-adipose replacement and loss of strength observed in patients.