Tezak Zivana, Hoffman Eric P, Lutz Jennica L, Fedczyna Tamara O, Stephan Dietrich, Bremer Eric G, Krasnoselska-Riz Irina, Kumar Ajit, Pachman Lauren M
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
J Immunol. 2002 Apr 15;168(8):4154-63. doi: 10.4049/jimmunol.168.8.4154.
Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA10501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21). We hypothesize that these data support a model of Ag (?viral) induction of an apparent autoimmune disease based on dynamic interaction between the muscle, vascular, and immune systems in the genetically susceptible (DQA10501(+)) child.
幼年皮肌炎（JDM）是最常见的儿童炎性肌病，是一种影响幼儿的系统性血管病。流行病学研究记录了JDM首个明确症状（皮疹和/或肌无力）出现前3个月内的前驱疾病，免疫数据支持这一研究，这些数据表明该疾病的病理生理学是由抗原驱动的。本研究的目的是比较4例未经治疗的DQA10501(+) JDM儿童肌肉活检中的基因表达谱与已知坏死性肌病（杜氏肌营养不良症）儿童、体外抗病毒模型（NF90）以及健康儿童对照的基因表达谱。JDM中近一半（47%）失调的基因与免疫反应相关。特别是，观察到IFN-αβ诱导基因6 - 16、抗黏液病毒蛋白p78、潜在胞质转录因子、LMP2和TAP1的表达增加。这一谱型与体外病毒抗性模型中所见的IFN-αβ转录级联一致。IFN-αβ诱导谱型叠加在与杜氏肌营养不良症共有的反映肌纤维坏死和再生的转录谱型上。通过定量实时PCR（6 - 16）、免疫荧光（血小板反应蛋白4）和免疫定位（IFN-γ、p21）对表达的基因进行了确认。我们推测，这些数据支持一种基于遗传易感（DQA10501(+)）儿童的肌肉、血管和免疫系统之间动态相互作用的抗原（？病毒）诱导明显自身免疫性疾病的模型。
