Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 16, Siena, 53100, Italy.
VA New York Harbor Healthcare System, 800 Poly Place, Brooklyn, New York 11209, USA.
Nat Rev Cardiol. 2017 Sep;14(9):521-535. doi: 10.1038/nrcardio.2017.61. Epub 2017 May 4.
Cardiac arrhythmias confer a considerable burden of morbidity and mortality in industrialized countries. Although coronary artery disease and heart failure are the prevalent causes of cardiac arrest, in 5-15% of patients, structural abnormalities at autopsy are absent. In a proportion of these patients, mutations in genes encoding cardiac ion channels are documented (inherited channelopathies), but, to date, the molecular autopsy is negative in nearly 70% of patients. Emerging evidence indicates that autoimmunity is involved in the pathogenesis of cardiac arrhythmias. In particular, several arrhythmogenic autoantibodies targeting specific calcium, potassium, or sodium channels in the heart have been identified. Experimental and clinical studies demonstrate that these autoantibodies can promote conduction disturbances and life-threatening tachyarrhythmias by inducing substantial electrophysiological changes. In this Review, we propose the term 'autoimmune cardiac channelopathies' to define this novel pathogenic mechanism of cardiac arrhythmias, which could be more frequent and clinically relevant than previously appreciated. Indeed, pathogenic autoantibodies against ion channels are detectable not only in patients with manifest autoimmune disease, but also in apparently healthy individuals, which suggests a causal role in some cases of unexplained arrhythmias and cardiac arrest. Considering this possibility and performing specific testing in patients with 'idiopathic' rhythm disturbances could create novel treatment opportunities.
在工业化国家，心律失常会导致相当大的发病率和死亡率。虽然冠状动脉疾病和心力衰竭是心脏骤停的常见原因，但在 5-15%的患者中，尸检时不存在结构异常。在这些患者中的一部分，记录了编码心脏离子通道的基因突变（遗传性通道病），但迄今为止，近 70%的患者的分子尸检结果为阴性。新出现的证据表明，自身免疫参与了心律失常的发病机制。特别是，已经鉴定出几种针对心脏特定钙、钾或钠通道的致心律失常自身抗体。实验和临床研究表明，这些自身抗体可通过诱导实质性电生理变化，促进传导障碍和危及生命的心动过速性心律失常。在这篇综述中，我们提出了“自身免疫性心脏通道病”这一术语来定义这种新的心律失常发病机制，它可能比以前认为的更常见且与临床更相关。事实上，针对离子通道的致病性自身抗体不仅可在有明显自身免疫性疾病的患者中检测到，也可在表面健康的个体中检测到，这表明在某些不明原因的心律失常和心脏骤停病例中具有因果关系。考虑到这种可能性，并在“特发性”节律紊乱患者中进行特定的检测，可能会为治疗带来新的机会。
