Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression
Allenbach Y., Leroux G., Suárez-Calvet X., Preusse C., Gallardo E., Hervier B., Rigolet A., Hie M., Pehl D., Limal N., Hufnagl P., Zerbe N., Meyer A., Aouizerate J., Uzunhan Y., Maisonobe T., Goebel HH., Benveniste O., Stenzel W., Hot A., Grados A., Schleinitz N., Gallet L., Streichenberger N., Petiot P., Hachulla E., Launay D., Devilliers H., Hamidou M., Cornec D., Bienvenu B., Langlois V., Levesque H., Delluc A., Drouot L., Charuel JL., Jouen F., Romero N., Dubourg O., Leonard-Louis S., Behin A., Laforet P., Stojkovic T., Eymard B., Costedoat-Chalumeau N., Campana-Salort E., Tournadre A., Musset L., Bader-Meunier B., Kone-Paut I., Sibilia J., Servais L., Fain O., Larroche C., Diot E., Terrier B., De Paz R., Dossier A., Menard D., Morati C., Roux M., Ferrer X., Martinet J., Besnard S., Bellance R., Cacoub P., Saadoun D., Arnaud L., Grosbois B., Herson S., Boyer O.
© 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.