Dalakas M C
Medical Neurology Branch, NINDS, NIH, Bethesda, MD 20892-1382, USA.
Ann Neurol. 1995 May;37 Suppl 1:S74-86. doi: 10.1002/ana.410370709.
Immune-mediated mechanisms appear to play a primary role in the pathogenesis of polymyositis (PM) and dermatomyositis (DM). The serum of patients with active DM has high levels of circulating complement fragments C3b, C4b, and C5b-9 membranolytic attack complex (MAC) and demonstrates a very high C3 uptake in an vitro assay system. The MAC and the immune complex-specific C3bNEO fragment are deposited on the endomysial capillaries early in the disease and lead sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis, and perifascicular atrophy. In contrast, in PM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize heretofore unknown and probably endogenous muscle antigens in the context of major histocompatibility complex (MHC) class I expression. A restricted (oligoclonal) pattern of T-cell receptor with prominence of Va1, Vb6, and Vb15 genes is noted within the endomysial infiltrates suggesting that the T-cell response is antigen driven. In both PM and DM, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are upregulated in the endomysial endothelial cells and function as ligands for the leukocyte integrins leukocyte function-associated antigen (LFA)-1 and very late activating antigen (VLA)-4, allowing activated lymphocytes to adhere to the endothelial cells and migrate to the muscle fibers. Among viruses, only the retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV)-1 have been convincingly shown to trigger PM, which is mediated by nonviral-specific, cytotoxic CD8+ cells. The treatment of inflammatory myopathies remains empirical. Many patients respond to steroids to some degree and for some period of time. Azathioprine, methotrexate, cyclosporine, cyclophosphamide, and plasmapheresis can be of mild to moderate benefit. High-dose intravenous immunoglobulin (IVIg) is a promising therapeutic modality for some patients resistant to therapies. In a controlled study, IVIg was effective in DM not only in improving the clinical symptoms but also in reversing the underlying immunopathology. The role of IVIg in PM and IBM is under study in control trials.
免疫介导机制似乎在多发性肌炎（PM）和皮肌炎（DM）的发病机制中起主要作用。活动期DM患者的血清中循环补体片段C3b、C4b和C5b-9膜攻击复合物（MAC）水平较高，并且在体外检测系统中表现出非常高的C3摄取。MAC和免疫复合物特异性C3bNEO片段在疾病早期沉积于肌内膜毛细血管，继而依次导致毛细血管丧失、肌肉缺血、肌纤维坏死和束周萎缩。相比之下，在PM中，肌纤维损伤由致敏的CD8+细胞毒性T细胞引发，这些T细胞在主要组织相容性复合体（MHC）I类表达的背景下识别迄今未知且可能是内源性的肌肉抗原。在肌内膜浸润中可观察到T细胞受体的受限（寡克隆）模式，其中Va1、Vb6和Vb15基因突出，提示T细胞反应是抗原驱动的。在PM和DM中，细胞间黏附分子（ICAM）-1和血管细胞黏附分子（VCAM）-1在肌内膜内皮细胞中上调，并作为白细胞整合素白细胞功能相关抗原（LFA）-1和极晚期活化抗原（VLA）-4的配体发挥作用，使活化的淋巴细胞能够黏附于内皮细胞并迁移至肌纤维。在病毒中，只有逆转录病毒人类免疫缺陷病毒（HIV）和人类嗜T细胞病毒（HTLV）-1已被确凿证明可引发PM，这由非病毒特异性的细胞毒性CD8+细胞介导。炎性肌病的治疗仍基于经验。许多患者在一定程度上和一段时间内对类固醇有反应。硫唑嘌呤、甲氨蝶呤、环孢素、环磷酰胺和血浆置换可能有轻度至中度益处。大剂量静脉注射免疫球蛋白（IVIg）对一些对其他治疗有抵抗的患者是一种有前景的治疗方式。在一项对照研究中，IVIg不仅在改善DM临床症状方面有效，而且在逆转潜在的免疫病理学方面也有效。IVIg在PM和包涵体肌炎（IBM）中的作用正在对照试验中进行研究。
