Penninger J M, Pummerer C, Liu P, Neu N, Bachmaier K
Amgen Institute/Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada.
APMIS. 1997 Jan;105(1):1-13. doi: 10.1111/j.1699-0463.1997.tb00532.x.
Dilated cardiomyopathy is a prevalent cause of progressive heart disease and sudden death, and most patients with cardiomyopathy have a history of viral myocarditis. Coxsackie B3 (CB3) picornaviruses can be detected in as many as 50% of these patients and CB3 infections have been epidemiologically linked to chronic heart disease. Several clinical and experimental studies suggest that chronic stages of disease are mediated by an autoimmune response against heart muscle myosin. Human heart disease can be mimicked in mice using cardiac myosin as autoantigen. Murine cardiac myosin-induced myocarditis is an organ-specific autoimmune disease and mediated by CD4+ T cells that recognize a myosin-specific peptide in association with MHC class II molecules. Here, the recent discovery of autoimmune epitopes derived from the alpha isoform of cardiac myosin, the functional roles of surface receptor and signal transduction molecules, and the molecular mechanisms of target organ susceptibility will be discussed.
扩张型心肌病是进展性心脏病和猝死的常见原因，大多数心肌病患者有病毒性心肌炎病史。在多达50%的此类患者中可检测到柯萨奇B3（CB3）微小核糖核酸病毒，并且CB3感染在流行病学上与慢性心脏病有关。多项临床和实验研究表明，疾病的慢性阶段是由针对心肌肌球蛋白的自身免疫反应介导的。使用心肌肌球蛋白作为自身抗原可在小鼠中模拟人类心脏病。鼠心肌肌球蛋白诱导的心肌炎是一种器官特异性自身免疫疾病，由与MHC II类分子相关联识别肌球蛋白特异性肽的CD4 + T细胞介导。在此，将讨论源自心肌肌球蛋白α同工型的自身免疫表位的最新发现、表面受体和信号转导分子的功能作用以及靶器官易感性的分子机制。
