Abstract

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 ╬▒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.

CONCLUSIONS

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 Hongliang Li et al in Journal of the American Heart Association, 26 February 2014

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