Autoimmune Basis for Postural Tachycardia Syndrome

作者：Li Hongliang; Yu Xichun; Liles Campbell; Khan Muneer; Vanderlinde Wood Megan; Galloway Allison; Zillner Caitlin; Benbrook Alexandria; Reim Sean; Collier Daniel; Hill Michael A; Raj Satish R; Okamoto Luis E; Cunningham Madeleine W; Aston Christopher E; Kem David C^*

来源：Journal of the American Heart Association, 2014, 3(1): e000755.

DOI：10.1161/JAHA.113.000755

• adrenergic receptor
• autoantibody
• autonomic function
• postural tachycardia syndrome

Background-Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR).
Methods and Results-Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for alpha 1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay. A receptor-transfected cell-based assay was used to detect the presence of beta 1AR and beta 2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69 +/- 3% compared to 91 +/- 1% of baseline for healthy controls, P<0.001) when coexisting beta 2AR dilative activity was blocked; and this was suppressed by alpha 1AR blockade with prazosin. POTS sera acted as a partial alpha 1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased beta 1AR activation (130 +/- 3% of baseline, P<0.01) and a subset had increased beta 2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced beta 1AR and beta 2AR agonist activity. Autoantibody-positive POTS sera demonstrated specific binding to beta 1AR, beta 2AR, and alpha 1AR in transfected cells.
Conclusions-POTS patients have elevated alpha 1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of alpha 1AR for vasoconstriction and concurrent beta AR-mediated tachycardia. Coexisting beta 1AR and beta 2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.

• 出版日期2014-2