545P Capillary abnormalities in immune-mediated necrotizing myopathy: more than collateral damage?

Immune-mediated necrotizing myopathy (IMNM) is a form of idiopathic inflammatory myopathy (IIM) characterized by severe, rapidly progressing muscle weakness, creatine kinase elevation and muscle fibre necrosis. IMNMs are divided into three subgroups depending on the presence of muscle specific autoantibodies: anti-SRP-positive, anti-HMGCR-positive and seronegative IMNM. Vascular abnormalities, particularly alterations in capillaries, have been mentioned in IMNM. However, the link between autoimmune muscle damage and abnormal capillary morphology has remained unclear. The type of capillary pathology is a relevant feature, since vascular damage is key e.g. in dermatomyositis and systemic sclerosis as highlighted recently. In this project, we aimed to characterize vascular/capillary abnormalities in muscle biopsies derived from HMGCR-Ab, SRP-Ab, and seronegative IMNM patients. Light and electron microscopy were used to assess structural changes in capillaries, while quantitative real-time PCR was used to study the expression of genes related to vascular function. Additionally, we analyzed the proteomic signature of IMNM in relation to vascularization. Distinct patterns of capillary abnormalities were identified in all IMNM subgroups. Capillaries showed a spectrum of alterations, including a broad range of basement membrane duplications, activation of endothelial subcellular organelles featuring vesicle formation, proliferation of pericytes and degeneration to string vessels, but they do not show endothelial tubuloreticular inclusions. By integrating these methods, this study sought to provide a comprehensive understanding of the vascular abnormalities observed in IMNM, shedding light on a previously neglected aspect of the disease's pathophysiology. [ABSTRACT FROM AUTHOR]