Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany.
Clin Immunol. 2010 Jan;134(1):80-8. doi: 10.1016/j.clim.2009.04.008. Epub 2009 May 14.
Despite the widespread use of cardiac troponins as biomarkers for the diagnosis and quantitation of cardiac injury, the effect of troponin release and a possible autoimmune response to the troponins is unknown. Other investigators reported that programmed cell death-1 (PD-1)-receptor deficient mice developed severe cardiomyopathy with autoantibodies to troponin I. We found that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. At later times, antibodies to cardiac myosin were detected in troponin-immunized mice. The severity of inflammation correlated with expression of chemokines RANTES, MIP-2, IP-10 and MCP-1 in the myocardium. Prior immunization with troponin I increased the severity of experimental infarctions, indicating that an autoimmune response to troponin I aggravates acute cardiac damage. Cardiac inflammation, fibrosis and functional impairment were transferred from immunized to naive recipients by CD4+ T cells, and the cytokine profile suggested both Th2 and Th17 profiles in A/J mice. Finally we identified an 18-mer of troponin I containing an immuno-dominant epitope.
尽管心肌肌钙蛋白已被广泛用作诊断和量化心脏损伤的生物标志物，但心肌肌钙蛋白的释放及其对免疫系统的可能影响尚不清楚。其他研究人员报告称，程序性细胞死亡受体-1（PD-1）缺陷型小鼠会产生严重的心肌病，伴有针对肌钙蛋白 I 的自身抗体。我们发现，用肌钙蛋白 I 而非肌钙蛋白 T 对具有遗传易感性的小鼠进行免疫接种，会引发强烈的自身免疫反应，导致心肌明显的炎症和纤维化。在稍后的时间，在肌钙蛋白免疫接种的小鼠中检测到针对心肌肌球蛋白的抗体。炎症的严重程度与心肌趋化因子 RANTES、MIP-2、IP-10 和 MCP-1 的表达相关。预先用肌钙蛋白 I 免疫接种会增加实验性梗死的严重程度，表明针对肌钙蛋白 I 的自身免疫反应会加重急性心脏损伤。心脏炎症、纤维化和功能障碍可通过 CD4+T 细胞从免疫接种的小鼠转移到未免疫的小鼠，细胞因子谱提示 A/J 小鼠存在 Th2 和 Th17 两种表型。最后，我们鉴定了肌钙蛋白 I 中含有免疫显性表位的 18 肽。
