Francesco Girolamo1, Anna Lia2, Tiziana Annese1, Margherita Giannini3, Angela Amati2, Dario D'Abbicco4, Marilina Tampoia5, Daniela Virgintino1, Domenico Ribatti1, Luigi Serlenga2, Florenzo Iannone3, Maria Trojano2. 1. Unit of Human Anatomy and Histology, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy. 2. Unit of Neurophysiopathology, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 3. Unit of Rheumatology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. 4. Institute of General Surgery "G Marinaccio", Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. 5. Unit of Clinical Pathology, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy.
Abstract
INTRODUCTION: 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.
INTRODUCTION: 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.