Activating autoantibodies to the beta 1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism

摘要

We have previously demonstrated that activating autoantibodies to beta 1-adrenergic receptor (beta 1AR) 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 beta 1AR, beta 2AR, 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. Sera from 20 ELISA-positive GD subjects, 10 with AF and 10 with sinus rhythm, were assayed for autoantibody bioactivity using cell-based bioassays. In patients with GD and AF, 45, 65, and 77 % were ELISA positive for beta 1AR, M2R, and beta 2AR autoantibodies, respectively. In patients with GD and sinus rhythm, 17, 39, and 75 % were ELISA positive for beta 1AR, M2R, and beta 2AR autoantibodies, respectively. beta 1AR and M2R autoantibodies were co-present in 39 % of patients with GD and AF compared to 14 % in GD with sinus rhythm (p = 0.026). Patients with toxic multinodular goiter or subacute thyroiditis had a low prevalence of autoantibodies. The mean beta 1AR and M2R autoantibody activity was elevated in both GD groups but higher in those with AF than those with sinus rhythm. beta 2AR autoantibody activity was also increased in both groups. In conclusion, beta 1AR, beta 2AR, and M2R autoantibodies were elevated in GD. beta 1AR and M2R autoantibodies appear to be related to concurrent AF, while beta 2AR autoantibodies were equally prevalent in those with a sinus tachycardia and those with AF.