Activating autoantibodies to the β1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism.

We have previously demonstrated that activating autoantibodies to β1-adrenergic receptor (β1AR) and M2 muscarinic receptor (M2R) facilitate atrial fibrillation (AF) in patients with Graves' disease (GD). The objectives of this expanded study were to examine the prevalence of β1AR, β2AR, and M2R autoantibodies in hyperthyroidism subjects. Sera from 81 patients including 31 with GD and AF, 36 with GD and sinus rhythm, 9 with toxic multinodular goiter, 5 with subacute thyroiditis, and 10 control subjects were examined for these autoantibodies by ELISA.

Autoimmune basis for 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 α1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay.

Autoimmune mechanisms activating the angiotensin AT1 receptor in 'primary' aldosteronism.

Context: The mechanisms causing excessive aldosterone production and hypertension in primary aldosteronism (PA) are complex and often incompletely recognized. Autoantibodies to the angiotensin AT1 receptor (AT1R) have been reported in some PA patients with an aldosterone-producing adenoma but not with idiopathic adrenal hyperplasia.

Objective: We investigated whether these autoantibodies will activate AT1R and thereby potentially contribute to the pathophysiology of PA.

Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism.

Agonistic autoantibodies to the β-adrenergic and muscarinic receptors are a novel investigative and therapeutic target for certain orthostatic disorders. We have identified the presence of autoantibodies to β2-adrenergic and/or M3 muscarinic receptors by ELISA in 75% (15 of 20) of patients with significant orthostatic hypotension. Purified serum IgG from all 20 of the patients and 10 healthy control subjects were examined in a receptor-transfected cell-based cAMP assay for β2 receptor activation and β-arrestin assay for M3 receptor activation.