ETIOLOGY AND PATHOGENESIS OF MYOPATHIES

特发性炎性肌病（多发性肌炎、皮肌炎和 相关疾病）是炎性疾病家族，其中 出现疾病特异性自身抗体， 间接证据表明是病毒引起的我们过去 几年来，观察和研究并收集血清，血液和肌肉 来自500多名疑似肌炎患者的样本， 我们收集了很多病人的流行病学资料。我们最近 注意力已经集中在自身免疫的机制上， 受影响肌肉内组织的细节。 我们已经完成了对另外两个主要序列的研究， 靶向自身抗原、异亮氨酰和（与Paul Schimmel合作 在麻省理工学院）丙氨酰-tRNA合成酶，并确定了染色体 四个目标氨酰-tRNA合成酶的位置。我们有 产生了纯的重组组氨酰-tRNA合成酶（HRS），并与克雷格 Hyde，制造了大的晶体，但是X射线衍射研究到目前为止 只有低分辨率。特里·奥汉伦博士和弗雷德·米勒博士 CBER/FDA与拉本博士，已经确定了一份似乎是 是线粒体HRS 我们已经研究了循环系统产生的细胞因子和趋化因子， 白细胞（与CBER/FDA的Dennis Klinman博士）和 影响肌肉活检，我们继续准备研究 在成肌细胞表面的I类HLA抗原中发现的肽。

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 500 patients suspected of having myositis and we have collected epidemiologic information on many patients. Our recent attention has been focussed on the mechanism of autoimmunity and on the details of tissue within the affected muscles. We have completed studies on the primary sequence of two more of the target autoantigens, isoleucyl- and (in collaboration with Paul Schimmel at MIT) alanyl-tRNA synthetase and have identified the chromosomal location of four of the target aminoacyl-tRNA synthetases. We have produced pure recombinant histidyl-tRNA synthetase (HRS) and, with Craig Hyde, made large crystals, but the x-ray diffraction studies have so far been of only low resolution. Dr. Terry O'Hanlon and Dr. Fred Miller of CBER/FDA with Dr. Raben, have identified a transcript of what appears to be the mitochondrial HRS. We have studied the cytokines and chemokines produced by circulating leukocytes (with Dr. Dennis Klinman of CBER/FDA) and by cells within affected muscle biopsies, and we have continued preparations to study the peptides found in Class I HLA antigens on the surface of myoblasts.