Introduction: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofibre protein degradation flux and muscle integrity, and has not been studied in IMNM. Methods: Muscle biopsies from patients with IMNM (n=40), dermatomyositis (DM, 24), polymyositis (PM, 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (sIBM, 8), and controls (6) were compared by immunohistochemistry. Results: The proportions of myofibres containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM, and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibres surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibres accumulated ubiquitin and misfolded protein. Discussion: The detection of LC3b+ or p62+ myofibres could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients outcomes.

Autophagy markers LC3 and p62 accumulate in immune‐mediated necrotizing myopathy

Tiziana, Annese;
2019

Abstract

Introduction: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofibre protein degradation flux and muscle integrity, and has not been studied in IMNM. Methods: Muscle biopsies from patients with IMNM (n=40), dermatomyositis (DM, 24), polymyositis (PM, 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (sIBM, 8), and controls (6) were compared by immunohistochemistry. Results: The proportions of myofibres containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM, and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibres surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibres accumulated ubiquitin and misfolded protein. Discussion: The detection of LC3b+ or p62+ myofibres could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients outcomes.
autophagy
complement membrane attack complex
MHC-II
necrotizing myopathy
ubiquitin
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.12572/8006
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