Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G-Protein Coupled Receptor Autoantibodies
Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G-Protein Coupled Receptor Autoantibodies
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DOI：
10.1161/jaha.119.013602
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发表时间：
2019-09-17
影响因子：
5.4
通讯作者：
Grubb, Blair P.
中科院分区：
文献类型：
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作者：
Gunning, William T., III;Kvale, Heather;Grubb, Blair P.
背景——体位性直立性心动过速综合征（POTS）的病因尚未确定。这种疾病经常被误诊为慢性焦虑症或恐慌症，因为这些患者的自主神经功能衰竭并不严重。越来越多的证据表明 POTS 可能是一种自身免疫性疾病。抗核抗体以及神经节、肾上腺素和毒蕈碱乙酰胆碱受体抗体的升高都有报道。方法和结果-我们收集了 55 名诊断为 POTS 的患者的详细临床症状。我们还通过 ELISA 评估了针对 4 种 G 蛋白偶联肾上腺素受体亚型和 5 种 G 蛋白偶联毒蕈碱乙酰胆碱受体亚型的自身抗体的血清水平。我们的患者有多种合并症，主要是年轻女性，并报告在晕厥发作前出现病毒样症状。我们检测到大量患者的肾上腺素 α 1 受体 (89%) 和毒蕈碱乙酰胆碱 M-4 受体 (53%) 自身抗体水平升高。令人惊讶的是，毒蕈碱受体自身抗体的升高似乎依赖于针对 A(1) 肾上腺素能受体的自身抗体的升高！在我们的研究中测量到，四名患者的 G 蛋白偶联自身抗体针对所有 9 种受体亚型均升高。 5 名 POTS 患者没有任何自身抗体升高；同样，对照的自身抗体升高也呈阴性。临床症状严重程度与 G 蛋白偶联自身抗体的相关性较弱。 结论——我们的观察提供了进一步的证据，表明在大多数情况下，POTS 患者至少有 1 种 G 蛋白偶联肾上腺素自身抗体升高，并且在某些情况下，肾上腺素能和毒蕈碱自身抗体同时存在，支持 POTS 可能是一种自身免疫性疾病的假设。
Background-The etiology of postural orthostatic tachycardia syndrome (POTS) is yet to be established. The disorder is often misdiagnosed as chronic anxiety or a panic disorder because the autonomic failure in these patients is not severe. A growing body of evidence suggests that POTS may be an autoimmune disorder. Antinuclear antibodies and elevations of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies have all been reported.Methods and Results-We collected detailed clinical symptoms of 55 patients diagnosed with POTS. We also evaluated serum levels of autoantibodies against 4 subtypes of G-protein coupled adrenergic receptors and 5 subtypes of G-protein coupled muscarinic acetylcholine receptors by ELISA. Our patients had a multitude of comorbidities, were predominantly young females, and reported viral-like symptoms preceding episodes of syncope. We detected a significant number of patients with elevated levels of autoantibodies against the adrenergic alpha 1 receptor (89%) and against the muscarinic acetylcholine M-4 receptor (53%). Surprisingly, elevations of muscarinic receptor autoantibodies appeared to be dependent upon elevation of autoantibodies against the A(1) adrenergic receptor! Four patients had elevations of G-protein coupled autoantibodies against all 9 receptor subtypes measured in our study. Five POTS patients had no elevation of any autoantibody; similarly, controls were also negative for autoantibody elevations. There was a weak correlation of clinical symptom severity with G-protein coupled autoantibodies.Conclusions-Our observations provide further evidence that, in most cases, POTS patients have at least 1 elevated G-protein coupled adrenergic autoantibody and, in some instances, both adrenergic and muscarinic autoantibodies, supporting the hypothesis that POTS may be an autoimmune disorder.