학술논문
Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies
Document Type
Article
Author
Allenbach, Yves; Leroux, Gaëlle; Suárez-Calvet, Xavier; Preusse, Corinna; Gallardo, Eduard; Hervier, Baptiste; Rigolet, Aude; Hie, Miguel; Pehl, Debora; Limal, Nicolas; Hufnagl, Peter; Zerbe, Norman; Meyer, Alain; Aouizerate, Jessie; Uzunhan, Yurdagul; Maisonobe, Thierry; Goebel, Hans-Hilmar; Benveniste, Olivier; Stenzel, Werner; Hot, Arnaud; Grados, Aurélie; Schleinitz, Nicolas; Gallet, Laure; Streichenberger, Nathalie; Petiot, Philippe; Hachulla, Eric; Launay, David; Devilliers, Hervé; Hamidou, Mohamed; Cornec, Divy; Bienvenu, Boris; Langlois, Vincent; Levesque, Hervé; Delluc, Aurélien; Drouot, Laurent; Charuel, Jean-Luc; Jouen, Fabienne; Romero, Norma; Dubourg, Odile; Leonard-Louis, Sarah; Behin, Anthony; Laforet, Pascal; Stojkovic, Tania; Eymard, Bruno; Costedoat-Chalumeau, Nathalie; Campana-Salort, Emmanuelle; Tournadre, Anne; Musset, Lucile; Bader-Meunier, Brigitte; Kone-Paut, Isabelle; Sibilia, Jean; Servais, Laurent; Fain, Olivier; Larroche, Claire; Diot, Elizabeth; Terrier, Benjamin; De Paz, Raphaël; Dossier, Antoine; Menard, Dominique; Morati, Chafika; Roux, Marielle; Ferrer, Xavier; Martinet, Jeremy; Besnard, Sophie; Bellance, Rémi; Cacoub, Patrice; Saadoun, David; Arnaud, Laurent; Grosbois, Bernard; Herson, Serge; Boyer, Olivier
Source
American Journal of Pathology; March 2016, Vol. 186 Issue: 3 p691-700, 10p
Subject
Language
ISSN
00029440
Abstract
The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti–MDA5+-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti–MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2–positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti–MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.