Antiadrenergic autoimmunity in postural tachycardia syndrome
Antiadrenergic autoimmunity in postural tachycardia syndrome
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DOI：
10.1093/europace/euw154
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发表时间：
2017-07-01
期刊：
影响因子：
6.1
通讯作者：
Kem, David C.
中科院分区：
文献类型：
--
作者：
Fedorowski, Artur;Li, Hongliang;Kem, David C.
体位性心动过速综合征（POTS）是一种常见的心血管疾病，其特征是体位性心率过快和肾上腺素能相关症状。为了确定POTS的病因，我们研究了针对α 1-肾上腺素能受体的自身抗体可能的病理生理作用。（α 1AR）和β 1/2-肾上腺素能受体免疫球蛋白G（IgG）来源于17名POTS患者，7名患有复发性血管迷走性晕厥（VVS），11名正常人分析了其调节α 1 AR和β 1/β 2 AR活性和配体反应性的能力。2 AR基因转染的细胞，并改变离体大鼠提睾肌小动脉的收缩性。在基于细胞的测定中，POTS中α 1 AR和β 1/2 AR的免疫球蛋白G活化显著高于VVS和对照。17例POTS患者中有8例、11例和12例分别具有激活α 1AR、β 1AR和β 2AR的自身抗体。药理学阻断抑制IgG诱导的α 1 AR和β 1/2 AR活化。17个POTS IgG中有8个降低了α 1 AR对苯肾上腺素的反应性，17个POTS IgG中有13个增加了β 1 AR对异丙肾上腺素的反应性，而不管它们直接激活受体的能力如何。体位性心动过速综合征IgG收缩大鼠提睾肌小动脉，α 1 AR阻滞可逆转。直立心率与IgG介导的β 1 AR和α 1 AR活性相关，但与β 2 AR活性无关。他们支持的概念，变构介导的转变，在α 1 AR和β 1 AR的反应性是重要的病理生理学的体位性心动过速。
Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against alpha 1-adrenergic (alpha 1AR) and beta 1/2-adrenergic receptors (beta 1/2AR).Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of alpha 1AR and beta 1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of alpha 1AR and beta 1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated alpha 1AR, beta 1AR and beta 2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of alpha 1AR and beta 1/2AR. Eight of 17 POTS IgG decreased the alpha 1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the beta 1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by alpha 1AR blockade. The upright heart rate correlated with IgG-mediated beta 1AR and alpha 1AR activity but not with beta 2AR activity.These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the alpha 1AR and beta 1AR responsiveness are important in the pathophysiology of postural tachycardia.