Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies Common Interferon Signature but Distinct NOS2 Expression
Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies Common Interferon Signature but Distinct NOS2 Expression
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DOI：
10.1016/j.ajpath.2015.11.010
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发表时间：
2016-03-01
影响因子：
6
通讯作者：
Stenzel, Werner
中科院分区：
文献类型：
--
作者：
Allenbach, Yves;Leroux, Gaelle;Stenzel, Werner
抗黑色素瘤分化相关基因5（MDA 5）自身抗体与皮肌炎（DM）特异性相关。尽管如此，抗-MDA 5（+）-患者经历不同于经典DM的特征性症状，包括肌外受累的严重体征;然而，肌病的临床体征是轻度的或甚至不存在。成年期的形态学和免疫学特征尚未描述。关于抗-MDA 5 DM的病理生理学的数据很少;然而，已经显示了干扰素（IFN）I型途径参与DM的重要性。我们的目的是确定骨骼肌的形态学改变和抗-MDA 5阳性DM患者的内在免疫应答。对抗-MDA 5和经典DM的肌肉活检标本进行免疫组织化学和RT-PCR分析。抗MDA 5 DM患者没有出现束周纤维萎缩和主要组织相容性复合物I类表达的经典特征。他们没有表现出显着的迹象毛细血管损失; tubuloreticular形成观察到的频率较低。炎症是局灶性的，聚集在单个血管周围，但明显不太严重。IFN刺激基因的表达在抗-MDA 5 DM中上调;然而，IFN评分显著降低。在抗MDA 5 DM中观察到特征性特征，而在经典DM患者中未观察到。只有抗-MDA 5 DM显示许多一氧化氮合酶2阳性肌纤维与再生和细胞应激标记的肌浆共定位。抗-MDA 5阳性患者表现出与经典DM不同的形态学模式。
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.