Xiao Hua, Wang Min, Du Yimei, Yuan Jing, Zhao Guanghong, Tu Danna, Liao Yu-Hua
Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, 430022 Wuhan, Hubei, China.
Heart Vessels. 2012 Sep;27(5):486-92. doi: 10.1007/s00380-011-0176-7. Epub 2011 Aug 4.
The calcium channel may be an important target in the autoimmune pathogenesis of dilated cardiomyopathy (DCM). The presence and function of serum autoantibodies against calcium channels (CC-AAbs) in patients with DCM were studied. Calcium-channel AAbs were detected in 80 patients with DCM and 80 controls by enzyme-linked immunosorbent assay (ELISA). Calcium-channel AAbs were further purified by affinity chromatography for characterization by immunoblotting and immunofluorescence. Voltage-clamp experiments were performed to identify the function of CC-AAbs. The presence of CC-AAbs was shown effectively by ELISA, and CC-AAbs were able specifically to bind to the calcium channel on the myocyte, confirmed by immunoblotting and immunofluorescence. Calcium currents were enhanced by CC-AAbs on Xenopus oocytes expressing human Ca(V)1.2 channels, which suggested CC-AAbs in patients with DCM were agonist-like. Our results suggest there are novel agonist-like CC-AAbs in patients with DCM. Calcium-channel AAbs might play an important role in the pathogenesis of DCM.
钙通道可能是扩张型心肌病（DCM）自身免疫发病机制中的一个重要靶点。本研究探讨了DCM患者血清中抗钙通道自身抗体（CC-AAbs）的存在情况及其功能。采用酶联免疫吸附测定（ELISA）法检测了80例DCM患者和80例对照者的钙通道自身抗体。通过亲和层析进一步纯化钙通道自身抗体，并用免疫印迹和免疫荧光法进行鉴定。进行电压钳实验以确定CC-AAbs的功能。ELISA法有效显示了CC-AAbs的存在，免疫印迹和免疫荧光证实CC-AAbs能够特异性结合心肌细胞上的钙通道。在表达人Ca(V)1.2通道的非洲爪蟾卵母细胞上，CC-AAbs增强了钙电流，这表明DCM患者的CC-AAbs具有类似激动剂的作用。我们的结果提示DCM患者存在新型的类似激动剂的CC-AAbs。钙通道自身抗体可能在DCM的发病机制中起重要作用。
