Spatial and cell type specific molecular genetic investigations of inflammatory myopathies with selective perifascicular injury.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic autoimmune disease often with multisystem involvement. Targeted therapy is still lacking. Efficient serum or histological markers to measure disease activity and predict disease course are missing. Perifascicular myofiber atrophy is a hall mark of dermatomyositis (DM). Despite decades of research, the mechanism of perifascicular atrophy is still incompletely understood. Across other IIM subtypes, perifascicular myofiber necrosis is also the hall mark pathology for antisynthetase syndrome associated myositis (ASyS)5, and can be seen in a subset of lupus myositis (LM). We hypothesize that direct comparison between tissue within the diseased perifascicular regions (PF) and the relatively normal centro-fascicular (CF) regions will help narrow down tissue specific drivers underlying the muscle injury (necrosis versus atrophy) in a disease specific manner.