G.P.60: Cytoplasmic 5′-nucleotidase 1A are aggregated in type 2 fiber in sporadic inclusion body myositis

Abstract

Although sporadic inclusion body myositis (sIBM) is classified as an inflammatory myopathy, it is thought to share common pathophysiology with other neurodegenerative diseases in terms of various aggregated proteins, such as TDP-43, amyloid-β, tau and optineurin. Recently, autoantibody targets Cytoplasmic 5′-nucleotidase 1A (NT5C1A) was identified in sera of sIBM patients, suggesting that NT5C1A is a key molecule in the pathogenesis of sIBM. To realize the impact of NT5C1A on the pathogenesis of sIBM, skeltal muscle biopsy samples of 11 patients with sIBM, 5 with polymyositis, 5 with dermatomyositis, 1 with oculopharyngeal muscular dystrophy and 2 healthy control subjects were histologically examined. In all samples from sIBM patients, NT5C1A aggregated in the cytoplasm and/or plasma membrane in small-sized myofibers which were frequently immunostained with fast-myosin heavy chain, a marker for type 2 muscle fiber. We also observed co-localization of NT5C1A with p62 in the perinuclei of some fibers. These findings suggest that functional and structural alteration of NT5C1A might affect the energy metabolism in the type 2 fibers. Co-localization of NT5C1A with p62 in the perinuclear region may indicate the involvement of deficit in nuclear function and protein degradation, suggesting the role of NT5C1A as a bridge between “inflammation” and “degeneration” in sIBM pathogenesis.