Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice
Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice
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DOI：
10.1038/nm955
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发表时间：
2003-12-01
期刊：
影响因子：
82.9
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Okazaki, T;Tanaka, Y;Honjo, T
我们最近报道，程序性细胞死亡 1 (PD-1) 免疫抑制辅助受体缺陷的小鼠会发展为自身免疫性扩张型心肌病 (DCM)，并产生针对心脏特异性 30 kDa 蛋白的高滴度自身抗体。在这项研究中，我们从心脏提取物中纯化了 30 kDa 的蛋白质，并将其鉴定为心肌肌钙蛋白 I (cTnI)，由一种基因编码，该基因的突变可导致家族性肥厚型心肌病 (HCM)。给予 cTnI 单克隆抗体可诱导野生型小鼠心脏扩张和功能障碍。 cTnI 单克隆抗体对心肌细胞表面进行染色，并增强正常心肌细胞的电压依赖性 L 型 Ca (2+) 电流。这些发现表明，cTnI 抗体通过长期刺激心肌细胞内 Ca2+ 流入而诱发心脏功能障碍和扩张。
We recently reported that mice deficient in the programmed cell death- 1 (PD- 1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high- titer autoantibodies against a heart- specific, 30- kDa protein. In this study, we purified the 30- kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild- type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage- dependent L- type Ca (2+) current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.