ETIOLOGY AND PATHOGENESIS OF IDIOPATHIC INFLAMMATORY MYOPATHY IN HUMANS

特发性炎症性肌病(多发性肌炎、皮肌炎和 相关疾病)是一类炎症性疾病，在这些疾病中- 会发生特定的自身抗体，对这种抗体有相当大的 间接证据指向病毒病因学。我们过去有过这样的经历 几年来，我观察、研究和收集了血清、血液和肌肉 来自450多名疑似肌炎患者的样本。我们 已经收集了许多患者的流行病学信息。我们有 克隆、测序和表达组氨酰-tRNA合成酶HRS， 特发性多发性肌炎和多发性肌炎的主要靶标自身抗原 皮肌炎和正在分析其结构和启动子。我们有 扩大对肌炎患者组的人类白细胞抗原分析 由使用序列特异性寡核苷酸的自身抗体定义 杂交/聚合酶链式反应方法。我们对HRS的启动子活性进行了分析 基因，目前正在研究其翻译控制 综合。我们成功地获得了HRS的高水平表达， 提纯了它，并使它结晶。一种灵敏、特异、稳定的酶联免疫吸附试验 已经开发出来，并申请了专利。 在特里·奥汉兰博士和弗雷德里克·米勒博士的合作下，我们 已经分析了T 一些肌炎患者肌肉中细胞受体的使用。

Idiopathic inflammatory myopathy (polymyositis, dermatomyositis, and related disorders) is a family of inflammatory diseases in which disease- specific autoantibodies occur and for which there is considerable indirect evidence pointing to a viral etiology. We have over the past several years, seen and studied and collected serum, blood, and muscle specimens from well over 450 patients suspected of having myositis. We have collected epidemiologic information on many patients. We have cloned, sequenced, and expressed histidyl-TRNA synthetase HRS, the principal target autoantigen in idiopathic polymyositis and dermatomyositis and are analyzing its structure and promoter. We have extended the analysis of HLA antigens in the sets of myositis patients defined by autoantibodies using the sequence specific oligonucleotide hybridization/PCR method. We have analyzed promoter activity of the HRS gene and are currently investigating translational control of its synthesis. We have successfully obtained high level expression of HRS, purified it, and crystallized it. A sensitive, specific, stable ELISA has been developed and a patent applied for. In collaboration with Dr. Terry O'Hanlan and Dr. Frederick Miller, we have analyzed T cell receptor usage in the muscle of some patients with myositis.