Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression

Yves Allenbach, Gaëlle Leroux, Xavier Suárez-Calvet, Corinna Preusse, Eduard Gallardo, Baptiste Hervier, Aude Rigolet, Miguel Hie, Debora Pehl, Nicolas Limal, Peter Hufnagl, Norman Zerbe, Alain Meyer, Jessie Aouizerate, Yurdagul Uzunhan, Thierry Maisonobe, Hans Hilmar Goebel, Olivier Benveniste, Werner Stenzel, Arnaud HotAurélie Grados, Nicolas Schleinitz, Laure Gallet, Nathalie Streichenberger, Philippe Petiot, Eric Hachulla, David Launay, Hervé Devilliers, Mohamed Hamidou, Divy Cornec, Boris Bienvenu, Vincent Langlois, Hervé Levesque, Aurélien Delluc, Laurent Drouot, Jean Luc Charuel, Fabienne Jouen, Norma Romero, Odile Dubourg, Sarah Leonard-Louis, Anthony Behin, Pascal Laforet, Tania Stojkovic, Bruno Eymard, Nathalie Costedoat-Chalumeau, Emmanuelle Campana-Salort, Anne Tournadre, Lucile Musset, Brigitte Bader-Meunier, Isabelle Kone-Paut, Jean Sibilia, Laurent Servais, Olivier Fain, Claire Larroche, Elizabeth Diot, Benjamin Terrier, Raphaël De Paz, Antoine Dossier, Dominique Menard, Chafika Morati, Marielle Roux, Xavier Ferrer, Jeremy Martinet, Sophie Besnard, Rémi Bellance, Patrice Cacoub, David Saadoun, Laurent Arnaud, Bernard Grosbois, Serge Herson, Olivier Boyer

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    65 Citations (Scopus)


    © Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. 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.
    Original languageEnglish
    Pages (from-to)691-700
    JournalAmerican Journal of Pathology
    Issue number3
    Publication statusPublished - 1 Mar 2016


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