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)是一种炎症性疾病家族， 疾病特异性自身抗体的发生有相当大的 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 样本来自超过375名怀疑患有肌炎的患者。我们 已经收集了许多患者的流行病学信息。我们有 组氨酰-tRNA合成酶HRS的克隆、测序和表达 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，并试图使它结晶(无论有没有 衬底)，以获得x射线晶体结构。我们有 成功克隆了一个突变型HRS，去掉了前两个外显子 目的探讨抗原性结构和tRNA结合情况。 我们在克隆异亮氨酸异亮氨酸和 亮氨酰tRNA合成。 利用重组的HRS，我们开发了一种技术来识别 慢性粒细胞白血病患者产生抗HRS自身抗体的个体B细胞 肌炎。我们正在分析使用的V区域 制造这些自身抗体的单个细胞。

Idiopathic inflammatory myopathy (polymyositis, dermatomyositis, and related disorders) is a family of inflammatory diseases in which disease-specific autoantibodies occur an 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 375 patients suspected of having myositis. We have collected epidemiologic information on many patients. We have cloned, sequences, 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 are attempting to crystallize it (with and without substrate) so as to obtain x-ray crystallographics structure. We have successfully cloned a mutant HRS with the first two exons removed in order to probe antigenic structure and tRNA binding. We have made substantial progress in attempts to clone isoleucyl and leucyl tRNA syntheses. Using recombinant HRS, we have developed a technique to identify individual B cell producing anti-HRS autoantibodies from patients with myositis. We are in the midst of an analysis of the V region used by individual cells making these autoantibodies.