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Am J Pathol. 2016 Mar;186(3):691-700. doi: 10.1016/j.ajpath.2015.11.010. Epub 2016 Jan 21.

Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression.

Author information

1
Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany; Department of Internal Medicine and Clinical Immunology and Inflammation, Immunopathology, and Biotherapy, Pierre et Marie Curie University, Paris, France; U974, INSERM, Sorbonne Universities, University Pierre et Marie-Curie, Paris, France. Electronic address: yves.allenbach@aphp.fr.
2
Department of Internal Medicine and Clinical Immunology and Inflammation, Immunopathology, and Biotherapy, Pierre et Marie Curie University, Paris, France.
3
Neuromuscular Diseases Unit, Neurology, Hospital de la Santa Creu I Sant Pau, Universita Autonoma de Barcelona and Institute de Recerca Sant Pau, Barcelona, Spain.
4
Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany.
5
Department of Internal Medicine and Clinical Immunology and Inflammation, Immunopathology, and Biotherapy, Pierre et Marie Curie University, Paris, France; U974, INSERM, Sorbonne Universities, University Pierre et Marie-Curie, Paris, France.
6
Department of Internal Medicine 2, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Universities, Pierre et Marie Curie University, Paris, France.
7
Department of Internal Medicine, Assistance Publique-Hôpitaux de Paris, Mondor Hospital, Creteil, France.
8
Department of Pathology, Charité-Universitätsmedizin, Berlin, Germany.
9
Department of Physiology, Strasbourg University Hospital, Strasbourg, France.
10
Department of Pathology, Mondor Hospital, Creteil, France.
11
Department of Pneumology Avicennes University Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France.
12
Department of Neuropathology, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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.

PMID:
26806087
DOI:
10.1016/j.ajpath.2015.11.010
[Indexed for MEDLINE]

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