Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression.
Am J Pathol
; 186(3): 691-700, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26806087
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dermatomiosite
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Óxido Nítrico Sintase Tipo II
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RNA Helicases DEAD-box
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Melanoma
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2016
Tipo de documento:
Article