Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy

Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy
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DOI:
10.1016/j.ehj.2004.05.012
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发表时间:
2004-07-01
影响因子:
39.3
通讯作者:
Fu, M
Fu, M
中科院分区:
医学1区
文献类型:
--
作者:
Baba, A;Yoshikawa, T;Fu, M

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目的 探讨M2-毒蕈碱型乙酰胆碱受体自身抗体(M2-AAB)在扩张型心肌病(DCM)患者中的临床意义。 方法与结果 采用酶联免疫吸附试验(ELISA)对104例DCM患者、年龄匹配的104例特发性房颤(Af)患者和104名健康对照者的血清进行M2-AAB筛查。通过 Protein-A 柱纯化的 IgG 也用作 ELISA 中的一抗。在 DCM 中,40% 使用全血清的患者检测到 M2-AAB,36% 使用纯化 IgG 的患者检测到 M2-AAB。 M2-AAB也在几名特发性房颤患者中发现(23%、23%),并且这些频率显着高于健康受试者(8%、8%)。 AAB 阳性 DCM 患者中 AAB 比 AAB 阴性更常见。多变量分析证实,M2-AAB 是此类患者存在 Af 的独立预测因子。我们通过将患者纯化的 M2-AAB 添加到鸡胚中来确定电生理变化。从Af和DCM患者中纯化的IgG均表现出负变时作用并诱发室上性心律失常。结论M2-AAB可能在介导DCM患者Af的发生过程中发挥作用。 (C) 2004 年欧洲心脏病学会。由爱思唯尔有限公司出版。保留所有权利。
Aim To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM).Methods and results Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias.Conclusion M2-AAB may play a rote in mediating the development of Af in patients with DCM. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.