Autoantibodies activating human β1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure
Autoantibodies activating human β1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure
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DOI：
10.1161/01.cir.99.5.649
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发表时间：
1999-02-09
期刊：
影响因子：
37.8
通讯作者：
Boege, F
中科院分区：
文献类型：
--
作者：
Jahns, R;Boivin, V;Boege, F
背景-在人类心肌病中已经观察到抗β-肾上腺素能受体合成肽的自身抗体。然而，它从来没有被证明，这样的抗体真的与天然的人β-肾上腺素能受体相互作用，也没有这样的相互作用的临床影响进行了调查，在较大的patients.Methods和结果，我们筛选了104例扩张性或缺血性心肌病（NYHA功能分级II至IV）和108名健康受试者的IgG抗体与β-受体肽反应。进一步分析此类IgG与天然重组人β-肾上腺素能受体的结合和功能相互作用。51%的患者存在与合成受体肽反应的抗体。然而，仅针对第二胞外受体结构域的亚组也识别位于细胞膜中的天然人β-肾上腺素能受体。该亚群的所有抗体均能破坏受体配体结合，增强受体介导的信号传导，并能被5 μ mol/L比索洛尔在体外阻断。它们在健康受试者中的患病率为1%，在缺血性心肌病中的患病率为10%，而在扩张性心肌病中的患病率为26%，并且与左心室功能显着较差有关。结论-我们的数据表明，针对人类β-肾上腺素能受体的激活自身抗体存在于大约25%的扩张性心肌病患者中。这种自身抗体的对抗可能有助于β-肾上腺素能受体阻滞剂在慢性心力衰竭中的有益作用。
Background-Autoantibodies against synthetic peptides of beta-adrenergic recehtors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human beta-adrenergic receptors, nor has the clinical impact of such an interaction been investigated in larger groups of patients.Methods and Results-We screened 104 patients with dilated or ischemic cardiomyopathy (NYHA functional classes II to IV) and 108 healthy subjects for IgG antibodies reacting with beta-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human beta-adrenergic receptors. Antibodies reacting with synthetic receptor peptides were present in 51% of the patients. However, only a subgroup directed against the second extracellular receptor domain also recognized native human beta-adrenergic receptors situated in a cell membrane. All antibodies of this subgroup impaired receptor ligand binding and enhanced receptor-mediated signaling, which could be blocked by 5 mu mol/L bisoprolol in vitro. Their prevalence was 1% in healthy subjects and 10% in ischemic cardiomyopathy, whereas it amounted to 26% in dilated cardiomyopathy and was associated with a significantly poorer left ventricular function.Conclusions-Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximate to 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.