Immunopathogenesis of inflammatory myopathies
Immunopathogenesis of inflammatory myopathies
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炎症性肌病的免疫发病机制
作者：
M. Dalakas
免疫介导的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。活动性DM患者的血清具有高水平的循环补体片段C3 b、C4 b和C5 b-9膜溶解攻击复合物（MAC），并在体外测定系统中显示出非常高的C3摄取。MAC和免疫复合物特异性C3 bNEO片段在疾病早期沉积在肌内膜毛细血管上，并依次导致毛细血管损失、肌肉缺血、肌纤维坏死和肌束周围萎缩。相比之下，在PM中，肌纤维损伤是由致敏的CD 8+细胞毒性T细胞启动的，所述细胞毒性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的且可能是内源性的肌肉抗原。在肌内膜浸润中观察到T细胞受体的限制性（寡克隆）模式，瓦尔、Vb 6和Vb 15基因突出，表明T细胞应答是抗原驱动的。在PM和DM中，细胞间粘附分子（ICAM）-1和血管细胞粘附分子（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，使活化的淋巴细胞粘附到内皮细胞并迁移到肌肉纤维。在病毒中，只有逆转录病毒人类免疫缺陷病毒（HIV）和人类T细胞嗜淋巴细胞病毒（HTLV）-I已令人信服地显示触发PM，其由非病毒特异性细胞毒性CD 8+细胞介导。炎性肌病的治疗仍然是经验性的。许多患者对类固醇有一定程度的反应，并持续一段时间。硫唑嘌呤、甲氨蝶呤、环孢霉素、环磷酰胺和血浆置换可产生轻度至中度获益。高剂量静脉注射免疫球蛋白（IVIg）是一种有前途的治疗方式，用于一些对治疗耐药的患者。在一项对照研究中，IVIg不仅在改善临床症状方面有效，而且在逆转潜在的免疫病理学方面也有效。IVIg在PM和IBM中的作用正在对照试验中研究。
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 Val, 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)‐I 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.
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DOI：
--
发表时间：
1992-07
期刊：
The American journal of pathology
影响因子：
--
作者：
V. Askanas;W. Engel;R. B. Alvarez
通讯作者：
V. Askanas;W. Engel;R. B. Alvarez
HTLV-I 多发性肌炎患者也感染了人类免疫缺陷病毒。
DOI：
10.1056/nejm198904133201507
发表时间：
1989
期刊：
The New England journal of medicine
影响因子：
--
作者：
Wiley,CA;Nerenberg,M;Cros,D;Soto-Aguilar,MC
通讯作者：
Soto-Aguilar,MC
炎症性肌病的细胞机制。
DOI：
--
发表时间：
1993
期刊：
Bailliere's clinical neurology
影响因子：
--
作者：
Hohlfeld,R;Goebels,N;Engel,AG
通讯作者：
Engel,AG
肌炎的免疫机制。
影响因子：
5.1
作者：
Targoff,IN
通讯作者：
Targoff,IN
影响因子：
3.3
作者：
ENGEL, AG;ARAHATA, K
通讯作者：
ARAHATA, K