Objective To determine the association between autoantibodies to G-protein-coupled receptors with effect on the cardiovascular system and the cardiac biomarker N-terminal pro-brain natriuretic peptide reflecting heart function in Gravesʼ disease. Design and Methods Sixty premenopausal women with Graves’ disease were analyzed for IgG autoantibodies against β1-adrenergic, muscarinic acetylcholine type 2 and angiotensin II type 1 receptors using enzyme-linked immunosorbent assays based on cell membranes overexpressing receptors in their native conformations. N-terminal pro-brain natriuretic peptide and heart symptoms were analyzed in hyperthyroidism and after 7.5 months of antithyroid treatment. Matched thyroid healthy controls were also assessed. Results Serum levels of antibodies against the β1-adrenergic and the muscarinic acetylcholine type 2 receptors were higher in hyperthyroid patients than in controls (median β1-adrenergic receptor antibodies 1.9 [IQR 1.3–2.7] vs. 1.1 [0.8–1.7] μg/mL, P<0.0001; muscarinic acetylcholine type 2 receptor 20.5 [14.0–38.3] vs. 6.0 [3.2–9.9] U/mL, P<0.0001). These antibodies decreased in euthyroidism (P<0.01), but were still higher than in controls (P<0.01). Angiotensin II type 1 receptor levels did not differ. N-terminal pro-brain natriuretic peptide was higher in hyperthyroidism (240 [134–372] vs. <35 [<35–67] ng/L, P<0.0001), normalized after treatment and did not correlate with autoantibodies. Conclusion Autoantibodies against the β1-adrenergic and the muscarinic acetylcholine type 2 receptors were increased in Graves’ patients, decreased with treatment, but did not correlate with cardiac function. However, an autoimmune effect on the heart cannot be excluded in subpopulations, as the functional properties of the analyzed antibodies remain to be determined.

中文翻译：

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β1-肾上腺素和毒蕈碱 2 型乙酰胆碱受体抗体在 Graves 甲状腺功能亢进症中增加，在抗甲状腺治疗期间减少

目的 确定 G 蛋白偶联受体自身抗体对心血管系统的影响以及反映 Graves 病心脏功能的心脏生物标志物 N 末端脑利钠肽前体之间的关系。设计和方法 使用酶联免疫吸附试验分析了 60 名患有 Graves 病的绝经前妇女针对 β1-肾上腺素能、毒蕈碱乙酰胆碱 2 型和血管紧张素 II 1 型受体的 IgG 自身抗体，该试验基于细胞膜在其天然构象中过表达受体。在甲状腺功能亢进和抗甲状腺治疗 7.5 个月后分析 N 端脑钠肽前体和心脏症状。还评估了匹配的甲状腺健康对照。结果 甲状腺功能亢进患者血清中β1-肾上腺素能和毒蕈碱乙酰胆碱2型受体的抗体水平高于对照组（β1-肾上腺素能受体抗体中位数为1.9 [IQR 1.3-2.7] vs. 1.1 [0.8-1.7] μg/mL , P<0.0001；毒蕈碱乙酰胆碱 2 型受体 20.5 [14.0–38.3] 与 6.0 [3.2–9.9] U/mL, P<0.0001)。这些抗体在甲状腺功能正常时降低（P<0.01），但仍高于对照组（P<0.01）。血管紧张素 II 1 型受体水平没有差异。N末端脑钠肽前体在甲状腺功能亢进症中较高（240 [134-372] vs. <35 [<35-67] ng/L，P<0.0001），治疗后正常化且与自身抗体无关。结论 Graves 患者的 β1-肾上腺素能受体和毒蕈碱乙酰胆碱 2 型受体自身抗体升高，随治疗而降低，但与心功能无关。然而，在亚群中不能排除对心脏的自身免疫效应，因为所分析抗体的功能特性仍有待确定。