Hirakata Michito
Department of Internal Medicine, Keio University School of Medicine.
Nihon Rinsho Meneki Gakkai Kaishi. 2007 Dec;30(6):444-54. doi: 10.2177/jsci.30.444.
The inflammatory muscle diseases, polymyositis (PM) and dermatomyositis (DM) are systemic connective tissue disorders characterized by chronic inflammation in skeletal muscle and involvement of various systemic organs. The pathogenesis of these heterogeneous diseases is unknown, but appear to mediate an autoimmune disorder that culminates in the tissue damage. Autoantibodies directed against various cellular constituents have been detected in patients with PM/DM, and 40-50% of patients have autoantibodies (myositis-specific antibodies : MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with characteristic clinical features and therefore provide us useful information for diagnosis, patient classification as well as predict of signs, symptoms of myositis, response to treatment, and prognosis. Autoantibodies to the cytoplasmic antigens, that are involved in protein synthesis or translation related proteins, are seen in patients with PM. Autoantibodies to eight of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "anti-synthetase syndrome." However, certain differences of the clinical features associated with each anti-synthetase have been noted, although their similarity is impressive. Anti-signal recognition particle antibodies are associated with severe, refractory myositis that differs significantly from anti-synthetase syndrome. Autoantibodies to the nuclear antigen, Mi-2 that is a transcription-regulating protein, are specifically seen in patients with DM responsive to corticosteroid therapy. In recent years, novel MSAs have been identified in clinically amyopathic dermatomyositis (anti-CADM-140 antibodies) and malignancy-associated myositis (anti-p155 and p155/p140 antibodies), in which autoantibodies have been thought to be negative. For understanding the pathogenic mechanisms of PM/DM, it is important to elucidate the relationship between these novel MSAs and their related clinical entities. Recently the nature of the target MSA autoantigens has been characterized using molecular biology and proteomic techniques. However, the mechanism of development of MSAs remains unknown. Further analysis of the molecular structure and biological function of target autoantigens recognized by these MSAs might provide the clues to the understanding of the etiology and pathogenesis of these disorders.
炎性肌病，即多发性肌炎（PM）和皮肌炎（DM），是系统性结缔组织疾病，其特征为骨骼肌的慢性炎症以及多个全身器官受累。这些异质性疾病的发病机制尚不清楚，但似乎介导了一种自身免疫性疾病，最终导致组织损伤。在PM/DM患者中已检测到针对各种细胞成分的自身抗体，40%至50%的患者具有自身抗体（肌炎特异性抗体：MSAs），这些抗体在肌炎患者中特异性存在。这些自身抗体与特征性临床特征密切相关，因此为我们提供了诊断、患者分类以及预测肌炎体征、症状、治疗反应和预后的有用信息。针对参与蛋白质合成或翻译相关蛋白质的细胞质抗原的自身抗体见于PM患者。针对八种氨酰tRNA合成酶的自身抗体各自与一种类似综合征相关，其特征为肌炎、间质性肺病、关节炎以及构成“抗合成酶综合征”的其他特征。然而，尽管每种抗合成酶相关的临床特征相似，但也已注意到某些差异。抗信号识别颗粒抗体与严重难治性肌炎相关，这与抗合成酶综合征有显著不同。针对核抗原Mi-2（一种转录调节蛋白）的自身抗体在对皮质类固醇治疗有反应的DM患者中特异性出现。近年来，在临床无肌病性皮肌炎（抗CADM-140抗体）和恶性肿瘤相关性肌炎（抗p155和p155/p140抗体）中发现了新的MSAs，而此前认为这些疾病中自身抗体应为阴性。为了解PM/DM的致病机制，阐明这些新的MSAs与其相关临床实体之间的关系很重要。最近，已使用分子生物学和蛋白质组学技术对目标MSA自身抗原的性质进行了表征。然而，MSAs的产生机制仍然未知。对这些MSAs识别的目标自身抗原的分子结构和生物学功能进行进一步分析，可能为理解这些疾病的病因和发病机制提供线索。
