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Exp Clin Endocrinol Diabetes 2021; 129(11): 783-790
DOI: 10.1055/a-1342-2853
Article

β1-adrenergic and Muscarinic Acetylcholine Type 2 Receptor Antibodies are Increased in Graves’ Hyperthyroidism and Decrease During Antithyroid Therapy

Karin Tammelin
1   Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
,
Anna Lundgren
2   Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
3   Institute of Biomedicine, Sahlgrenska Academy, Department of Microbiology and Immunology, University of Gothenburg, Sweden
,
Mats Holmberg
1   Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
4   ANOVA, Karolinska University Hospital, Stockholm, Sweden
,
Bengt Andersson
2   Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
,
Helena Filipsson Nyström
1   Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
5   Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
6   Wallenberg Center for Molecular and Translational Medicine, Gothenburg, Sweden
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Abstract

Objective To determine the association between autoantibodies to G-protein-coupled receptors with effect on the cardiovascular system and the cardiac biomarker N-terminal pro-brain natriuretic peptide reflecting heart function in Gravesʼ disease.

Design and Methods Sixty premenopausal women with Graves’ disease were analyzed for IgG autoantibodies against β1-adrenergic, muscarinic acetylcholine type 2 and angiotensin II type 1 receptors using enzyme-linked immunosorbent assays based on cell membranes overexpressing receptors in their native conformations. N-terminal pro-brain natriuretic peptide and heart symptoms were analyzed in hyperthyroidism and after 7.5 months of antithyroid treatment. Matched thyroid healthy controls were also assessed.

Results Serum levels of antibodies against the β1-adrenergic and the muscarinic acetylcholine type 2 receptors were higher in hyperthyroid patients than in controls (median β1-adrenergic receptor antibodies 1.9 [IQR 1.3–2.7] vs. 1.1 [0.8–1.7] μg/mL, P<0.0001; muscarinic acetylcholine type 2 receptor 20.5 [14.0–38.3] vs. 6.0 [3.2–9.9] U/mL, P<0.0001). These antibodies decreased in euthyroidism (P<0.01), but were still higher than in controls (P<0.01). Angiotensin II type 1 receptor levels did not differ. N-terminal pro-brain natriuretic peptide was higher in hyperthyroidism (240 [134–372] vs. <35 [<35–67] ng/L, P<0.0001), normalized after treatment and did not correlate with autoantibodies.

Conclusion Autoantibodies against the β1-adrenergic and the muscarinic acetylcholine type 2 receptors were increased in Graves’ patients, decreased with treatment, but did not correlate with cardiac function. However, an autoimmune effect on the heart cannot be excluded in subpopulations, as the functional properties of the analyzed antibodies remain to be determined.

Key words

autoantibodies - G-protein-coupled receptor - β1 receptor - angiotensin II type 1 receptor - muscarinic type 2 receptor - cardiac biomarkers

Supplementary Material



Publication History

Received: 28 September 2020
Received: 02 December 2020

Accepted: 22 December 2020

Article published online:
12 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
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