Cardiac β1-adrenoceptor autoantibodies in human heart disease: rationale and design of the Etiology, Titre-Course, and Survival (ETiCS) Study
Cardiac β1-adrenoceptor autoantibodies in human heart disease: rationale and design of the Etiology, Titre-Course, and Survival (ETiCS) Study
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DOI：
10.1093/eurjhf/hfq072
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发表时间：
2010-07-01
影响因子：
18.2
通讯作者：
Jahns, Roland
中科院分区：
文献类型：
--
作者：
Deubner, Nikolas;Berliner, Dominik;Jahns, Roland
在过去几年中，自身免疫与人类心脏病的病理生理学相关性的证据大幅增加。刺激心脏 β 1-肾上腺素受体 (β 1-aabs) 的构象自身抗体被认为在心力衰竭的发展中具有重要意义，临床试验研究已显示其在人类“特发性”心肌病中的预后意义。我们最近开发了一种新型高灵敏度的基于荧光的功能测定法来检测刺激性 β 1-aabs。我们将在一项前瞻性多中心研究中使用这种方法来评估 β1-aab 的病因、滴度进程和对生存的影响 (ETiCS)，并对首次急性心肌炎或心肌梗死后的患者进行连续随访。几个欧洲核心实验室将联合研究以下假设：这两种疾病可能引发自身免疫反应，从而导致 β1-aab 和/或其他心脏导向的 aab 的产生。此外，将对来自健康对照和特征明确的扩张型、缺血性或高血压性心肌病患者队列的血清进行回顾性分析，以了解 β1-aab 的患病率、发生率、持续性和/或清除率。ETiCS 是迄今为止最大的旨在解决心脏自身免疫问题的临床诊断研究。它试图揭示心脏自身抗体形成和持续/清除的病理生理学。 ETiCS 将增强当前对人类心脏病自身免疫的了解，并促进开发针对心脏 aab 的新疗法。
Evidence for a pathophysiologic relevance of autoimmunity in human heart disease has substantially increased over the past years. Conformational autoantibodies stimulating the cardiac beta 1-adrenoceptor (beta 1-aabs) are considered of importance in heart failure development and clinical pilot studies have shown their prognostic significance in human 'idiopathic' cardiomyopathy.We recently developed a novel highly sensitive fluorescence-based functional assay to detect stimulating beta 1-aabs. We will use this method to assess Etiology, Titre-Course, and effect on Survival (ETiCS) of beta 1-aabs in a prospective multicentre study with serial follow-up of patients after a first acute myocarditis or myocardial infarction. Several European core laboratories will jointly study the hypothesis that both disorders may trigger autoimmune reactions leading to the generation of beta 1-aabs and/or other heart-directed aabs. Further, sera from healthy controls and well-characterized patient cohorts with dilated, ischaemic, or hypertensive cardiomyopathy will be analysed retrospectively for beta 1-aab prevalence, incidence, persistence, and/or clearance.ETiCS is so far the largest clinical diagnostic study projected to address cardiac autoimmunity. It attempts to unravel the pathophysiology of cardiac autoantibody formation and persistence/clearance. ETiCS will enhance current knowledge on autoimmunity in human heart disease and promote endeavours to develop novel therapies targeting cardiac aabs.