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cDNA microarrays reveal distinct gene expression clusters in idiopathic inflammatory myopathies

机译:cDNA微阵列揭示特发性炎症性肌病中不同的基因表达簇

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Background:Polymyositis (PM) and dermatomyositis (DM) are complex human diseases of autoimmune origin which cause progressive skeletal muscle weakness in adults and children. Histopathological studies of affected muscles suggest that cytotoxic T cell-induced injury predominates in PM, while humoral immune mechanisms seem more likely in DM. Early expression of MHC class I molecules on myocytes is a striking feature of both disorders. This study was to use gene microarray analysis of muscle biopsies from PM and DM patients to obtain a comprehensive view of molecules participating in disease pathogenesis.Material/Methods:Muscle biopsies from 10 patients (6 PM and 4 DM) and 5 controls were selected for gene expression profiles. Microarray filters containing 4000 known human genes were used to hybridize with RNAs from muscle biopsies. Real-time RT-PCR assays were used to confirmed selected genes that showed changes in expression levels in PM and DM from microarray data. The t-statistic was used to measure any differences in the amount of gene expression in the normal versus myositis biopsies.Results:Forty genes clustering into two major groups showed significantly altered expression levels in PM/DM compared to normal biopsies. One cluster of over-expressed genes was primarily of immune origin and included HLA-class I and II, interferon-inducible proteins, natural killer (NK) protein, immunoglobulins and complement. The other cluster of under-expressed genes were of muscle origin, especially those involved in the fast twitch response. PM and DM gene profiles appeared similar.Conclusions:PM and DM muscle biopsies show similar gene expression profiles despite reported differences in histopathological changes. Altered gene expressions of immune regulation and myofibrillar proteins are prominent in muscle biopsies of myositis.
机译:背景:多发性肌炎(PM)和皮肌炎(DM)是人类自身免疫性疾病的复杂人类疾病,可导致成年人和儿童进行性骨骼肌无力。对受累肌肉的组织病理学研究表明,PM中细胞毒性T细胞诱导的损伤占主导,而DM中体液免疫机制似乎更可能。 MHC I类分子在肌细胞上的早期表达是两种疾病的显着特征。这项研究将使用PM和DM患者肌肉活检的基因芯片分析来全面了解参与疾病发病机制的分子。材料/方法:选择10例患者(6 PM和4 DM)和5名对照进行肌肉活检基因表达谱。包含4000个已知人类基因的微阵列过滤器用于与肌肉活检组织的RNA杂交。实时RT-PCR分析用于确认选定的基因,这些基因显示了来自微阵列数据的PM和DM中表达水平的变化。 t统计量用于测量正常和肌炎活检中基因表达量的任何差异。结果:与正常活检相比,聚类为两个主要组的40个基因显示PM / DM中的表达水平发生了显着变化。一类过表达的基因主要是免疫起源的,包括HLA I类和II类,干扰素诱导蛋白,自然杀伤(NK)蛋白,免疫球蛋白和补体。另一组表达不足的基因是肌肉起源的,尤其是那些参与快速抽搐反应的基因。结论:PM和DM肌肉活检组织显示相似的基因表达谱,尽管据报道组织病理学改变存在差异。免疫调节和肌原纤维蛋白的基因表达改变在肌炎的肌肉活检中很明显。

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