Implications of Antimuscarinic Autoantibodies in Postural Tachycardia Syndrome,Journal of Cardiovascular Translational Research

当前位置： X-MOL 学术 › J. of Cardiovasc. Trans. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Implications of Antimuscarinic Autoantibodies in Postural Tachycardia Syndrome
Journal of Cardiovascular Translational Research ( IF 2.4 ) Pub Date : 2021-08-18 , DOI: 10.1007/s12265-021-10167-z
Hongliang Li ₁ , Gege Zhang ₁ , Elizabeth Forsythe ₁ , Luis E Okamoto ₂ , Xichun Yu ₁

Affiliation

Functional autoantibodies directed to the M2 muscarinic acetylcholine receptor (M2R) could affect the heart rate directly by altering cardiac M2R activity and/or indirectly by changing vagal-mediated cardiac M2R activity. We measured M2R autoantibody activity in sera from 10 subjects with postural tachycardia syndrome (POTS) and 5 healthy control subjects using a cell-based bioassay. Half of the POTS subjects demonstrated presence of elevated M2R autoantibody activity, while no significant M2R autoantibody activity was found in the healthy subjects. Serum-derived immunoglobulin G (IgG) from antibody-positive POTS patients induced a dose-dependent activation of M2R, which was blocked by the muscarinic antagonist atropine. Moreover, antibody-positive POTS IgG decreased the responsiveness to oxotremorine, an orthosteric muscarinic agonist, indicating an indirect inhibitory effect. These data suggest that M2R autoantibodies may contribute to the pathophysiology of POTS by increasing the normal vagal withdrawal during upright posture through its negative allosteric modulation of M2R activity.

Graphical abstract

M2 muscarinic receptor-activating autoantibodies are present in a subgroup of patients with POTS and act as a negative allosteric modulator of the orthosteric ligand response

中文翻译：

抗毒蕈碱自身抗体在体位性心动过速综合征中的意义

针对 M2 毒蕈碱性乙酰胆碱受体 (M2R) 的功能性自身抗体可通过改变心脏 M2R 活性直接影响心率和/或通过改变迷走神经介导的心脏 M2R 活性间接影响心率。我们使用基于细胞的生物测定法测量了 10 名体位性心动过速综合征 (POTS) 受试者和 5 名健康对照受试者血清中的 M2R 自身抗体活性。一半的 POTS 受试者表现出 M2R 自身抗体活性升高，而在健康受试者中未发现显着的 M2R 自身抗体活性。来自抗体阳性 POTS 患者的血清衍生免疫球蛋白 G (IgG) 诱导 M2R 的剂量依赖性激活，其被毒蕈碱拮抗剂阿托品阻断。此外，抗体阳性 POTS IgG 降低了对正构毒蕈碱激动剂氧代震颤素的反应性，表明有间接抑制作用。这些数据表明，M2R 自身抗体可能通过其对 M2R 活性的负变构调节增加直立姿势期间的正常迷走神经收缩，从而促进 POTS 的病理生理学。