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 ╬▒1AR autoantibodyÔÇÉmediated contractility using a perfused rat cremaster arteriole assay. A receptorÔÇÉtransfected cellÔÇÉbased assay was used to detect the presence of ╬▓1AR and ╬▓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 ╬▓2AR dilative activity was blocked; and this was suppressed by ╬▒1AR blockade with prazosin.
POTS sera acted as a partial ╬▒1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased ╬▓1AR activation (130┬▒3% of baseline, P<0.01) and a subset had increased ╬▓2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced ╬▓1AR and ╬▓2AR agonist activity. AutoantibodyÔÇÉpositive POTS sera demonstrated specific binding to ╬▓1AR, ╬▓2AR, and ╬▒1AR in transfected cells.
POTS patients have elevated ╬▒1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of ╬▒1AR for vasoconstriction and concurrent ╬▓ARÔÇÉmediated tachycardia. Coexisting ╬▓1AR and ╬▓2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.
Autoimmune Basis for Postural Tachycardia Syndrome, by┬áHongliang Li et al in Journal of the American Heart Association, 26 February 2014