Epitope Heterogeneity of Thyroid-Stimulating Antibodies Predicts Long-Term Outcome in Graves’ Patients Treated with Antithyroid Drugs

Author:

Kim Tae Yong1,Park Young Joo1,Park Do Joon1,Chung Hyun-Kyung2,Kim Won Bae3,Kohn Leonard D.4,Cho Bo Youn1

Affiliation:

1. Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital (T.Y.K., Y.J.P., D.J.P., B.Y.C.), Seoul 110-744, Korea

2. Department of Internal Medicine, Dankook University College of Medicine (H.C.), Cheonan 330-715, Korea

3. Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine (W.B.K.), Seoul 110-744, Korea

4. Edison Biotechnology Institute and Ohio University College of Osteopathic Medicine (L.D.K.), Athens, Ohio 45701

Abstract

Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from patients with untreated Graves’ disease were compared with long-term response to antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras, wherein TSHR residues 9–165 or 90–165 had been substituted with comparable residues of the LH/chorionic gonadotropin receptor. Of 159 patients studied, 52 (32.7%) exhibited positive TSAb activity with one or both chimera lines (heterogeneous group), and 107 (67.3%) had no activity with either (homogeneous group). Independent of all other parameters, patients with heterogeneous epitopes responded more favorably to oral antithyroid drugs than patients with homogeneous epitopes (65.4% vs. 41.9%, P = 0.011: estimated odds ratio by logistic regression, 2.17). Although most clinical parameters were not different at presentation, significant differences in the size of goiters, total T3 concentrations, and titers of TSH-binding inhibitory Igs were evident in the successfully treated group (n = 80) by comparison to the group of patients whose treatment failed (n = 79). Alone, these three parameters did not predict outcome; however, when either of these parameters were considered together with epitope heterogeneity, predictability of a positive therapeutic response was increased to nearly 80%. Thus, the presence of TSAbs with a heterogeneous epitope in a patient with Graves’ disease is not only associated with a favorable response to antithyroid drug treatment, it may help predict the response to treatment when the patient is initially seen.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference26 articles.

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2. Thyroid controversy—stimulating antibodies.;Davies;J Clin Endocrinol Metab,1998

3. Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves’ disease.;Feldt-Rasmussen;J Clin Endocrinol Metab,1994

4. Immunoglobulins from Graves’ disease patients interact with different sites on TSH receptor/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients.;Tahara;Biochem Biophys Res Commun,1991

5. Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.;Nagayama;J Clin Invest,1991

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