title: Activating autoantibodies to the β1/2-adrenergic and M2 muscarinic receptors associate with atrial tachyarrhythmias in patients with hyperthyroidism.
abstract: 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. 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 β1AR, M2R, and β2AR autoantibodies, respectively. In patients with GD and sinus rhythm, 17, 39, and 75 % were ELISA positive for β1AR, M2R, and β2AR autoantibodies, respectively. β1AR 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 β1AR and M2R autoantibody activity was elevated in both GD groups but higher in those with AF than those with sinus rhythm. β2AR autoantibody activity was also increased in both groups. In conclusion, β1AR, β2AR, and M2R autoantibodies were elevated in GD. β1AR and M2R autoantibodies appear to be related to concurrent AF, while β2AR autoantibodies were equally prevalent in those with a sinus tachycardia and those with AF.
authors.affiliation: Endocrinology and the Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Galloway
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Megan
authors.initials: M
authors.lastname: Vanderlinde-Wood
authors.forename: Muneer
authors.initials: M
authors.lastname: Khan
authors.forename: Alexandria
authors.initials: A
authors.lastname: Benbrook
authors.forename: Campbell
authors.initials: C
authors.lastname: Liles
authors.forename: Caitlin
authors.initials: C
authors.lastname: Zillner
authors.forename: Veitla
authors.initials: V
authors.lastname: Rao
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Xichun
authors.initials: X
authors.lastname: Yu
authors.forename: David C
authors.initials: DC
authors.lastname: Kem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood* / Q000209:etiology; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D043585:Receptor, Muscarinic M2 / Q000276:immunology*; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology*; D013610:Tachycardia / Q000097:blood* / Q000209:etiology
chemical_list: D001323:Autoantibodies; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2