Note: You can read the full study HERE.
By Hongliang Li, MD et al.
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 alpha1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay. A receptor-transfected cell-based assay was used to detect the presence of beta1AR 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 alpha1AR antagonist significantly shifting phenylephrine contractility curves to the right.
All POTS sera increased beta1AR activation (130±3% of baseline, P<0.01) and a subset had increased beta2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced beta1AR and beta2AR agonist activity. Autoantibody-positive POTS sera demonstrated specific binding to beta1AR, beta2AR, and alpha1AR in transfected cells.
Conclusions: POTS patients have elevated alpha1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of alpha1AR for vasoconstriction and concurrent betaAR-mediated tachycardia. Coexisting beta1AR 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.
Source: Hongliang Li, MD, PhD; Xichun Yu, MD; Campbell Liles, BS; Muneer Khan, MD; Megan Vanderlinde-Wood, MD; Allison Galloway, MD; Caitlin Zillner, BS; Alexandria Benbrook, BS; Sean Reim, BS; Daniel Collier, BS; Michael A. Hill, PhD; Satish R. Raj, MD; Luis E. Okamoto, MD; Madeleine W. Cunningham, PhD; Christopher E. Aston, PhD; David C. Kem, MD, Autoimmune Basis for Postural Tachycardia Syndrome (POTS). J Am Heart Assoc. 2014; 3: e000755 originally published February 26, 2014, doi: 10.1161 JAHA.113.000755