Department of Internal Medicine B and Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Ramat-Gan, 52621, Israel.
Clin Rev Allergy Immunol. 2012 Jun;42(3):298-308. doi: 10.1007/s12016-010-8235-x.
The role of autoimmunity in cardiovascular diseases has become one of the focal points of research studies. Autoimmune response and autoreactive autoantibodies have been found in dilated cardiomyopathy, heart failure, rheumatic fever, myocarditis, atherosclerosis, and other diseases. Autoantibodies may appear due to tissue injury and exposure of autoantigens, in addition to molecular mimicry and cross-reactivity with antigens found in infectious agents in predisposed individuals. In the early 1990s, autoantibodies reacting with the M2 muscarinic receptor were found in patients with dilated cardiomyopathy and subsequently, in patients with Chagas heart disease and arrhythmic disorders. Immunization of animals with the corresponding antigen triggered cardiac abnormalities also appearing in dilated cardiomyopathy of humans. It has been suggested that antibodies against M2 muscarinic receptors play a role in the pathogenesis of cardiac diseases and may also alter the electrophysiological properties of cardiac tissue. Herein, we review the current knowledge of antibodies against M2 muscarinic receptors and the possible use of a targeted therapy against these autoantibodies.
自身免疫在心血管疾病中的作用已成为研究的焦点之一。在扩张型心肌病、心力衰竭、风湿热、心肌炎、动脉粥样硬化等疾病中发现了自身免疫反应和自身反应性自身抗体。除了分子模拟和与易感性个体中感染因子中发现的抗原交叉反应之外,自身抗体可能由于组织损伤和自身抗原暴露而出现。在 20 世纪 90 年代初,在扩张型心肌病患者中发现了与 M2 毒蕈碱受体反应的自身抗体,随后在恰加斯心脏病和心律失常患者中也发现了该自身抗体。用相应抗原对动物进行免疫接种也会引发人类扩张型心肌病中出现的心脏异常。有人认为,抗 M2 毒蕈碱受体抗体在心脏疾病的发病机制中起作用,并且还可能改变心脏组织的电生理特性。本文综述了目前关于 M2 毒蕈碱受体抗体的知识,以及针对这些自身抗体的靶向治疗的可能应用。