Tsui F W, Siminovitch K A
Department of Medicine, University of Toronto, Ontario, Canada.
Int Rev Immunol. 1991;7(3):225-35. doi: 10.3109/08830189109061776.
Polymyositis and dermatomyositis are inflammatory myopathies characterized by proximal muscle weakness and myopathic electromyographic and histological findings. While the causes of myositis are not known, the close association of these disorders with a spectrum of autoantibodies suggests an etiologic and/or pathogenetic role for autoimmune processes. Of particular interest in this regard are antibodies directed against histidyl as well as other tRNA synthetases which are almost uniquely associated with myositis and may define a distinct subset of patients. Recently we isolated the histidyl tRNA synthetase gene which encodes the autoantigen representing the most frequent target of the myositis autoimmune response. The isolation and expression of this gene has allowed us to investigate both the autoreactive epitopes on histidyl-tRNA synthetase and the extent to which these correlate with functional epitopes on the molecule. As described here, the results of these studies as well as other recent data pertaining to the immunopathogenesis of myositis, provide a framework for delineating the mechanisms which render synthetases and other translation-related proteins autoantigenic in myositis, and allow one to examine the significance of such autoimmune responses in the etiology and pathogenesis of inflammatory myopathy.
多发性肌炎和皮肌炎是炎性肌病，其特征为近端肌无力以及肌病性肌电图和组织学表现。虽然肌炎的病因尚不清楚，但这些疾病与一系列自身抗体的密切关联提示自身免疫过程在病因学和/或发病机制中起作用。在这方面，特别令人感兴趣的是针对组氨酰tRNA合成酶以及其他tRNA合成酶的抗体，这些抗体几乎仅与肌炎相关，可能定义了一个独特的患者亚群。最近我们分离出了组氨酰tRNA合成酶基因，该基因编码自身抗原，而该自身抗原是肌炎自身免疫反应最常见的靶点。该基因的分离和表达使我们能够研究组氨酰tRNA合成酶上的自身反应性表位以及这些表位与该分子上功能表位的相关程度。如下所述，这些研究结果以及其他有关肌炎免疫发病机制的最新数据，为描绘使合成酶和其他与翻译相关的蛋白质在肌炎中成为自身抗原的机制提供了一个框架，并使人们能够研究这种自身免疫反应在炎性肌病的病因学和发病机制中的意义。
