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Autophagy markers LC3 and p62 accumulate in immune‐mediated necrotizing myopathy
Author(s) -
Girolamo Francesco,
Lia Anna,
Annese Tiziana,
Giannini Margherita,
Amati Angela,
D'Abbicco Dario,
Tampoia Marilina,
Virgintino Daniela,
Ribatti Domenico,
Serlenga Luigi,
Ian Florenzo,
Trojano Maria
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26608
Subject(s) - polymyositis , autophagy , dermatomyositis , myocyte , inclusion body myositis , myopathy , myositis , creatine kinase , ubiquitin , biology , immunohistochemistry , pathology , medicine , microbiology and biotechnology , apoptosis , endocrinology , biochemistry , gene
: The molecular mechanism of immune‐mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber 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 (8), and controls (6) were compared by immunohistochemistry. Results : The proportions of myofibers 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 myofibers surrounded by major histocompatibility complex type II + inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. Discussion : The detection of LC3b + or p62 + myofibers could be used in differentiating IMNM from PM. The identification of autophagy‐modifying molecules potentially could improve patients’ outcomes. Muscle Nerve , 2019