title: Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Graves' patients treated with antithyroid drugs.
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 T(3) 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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Chung
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Kohn
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000627:therapeutic use*; D016466:CHO Cells; D002460:Cell Line; D002678:Chimera; D006224:Cricetinae; D000939:Epitopes; D005544:Forecasting; D014644:Genetic Variation; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology*; D011974:Receptors, LH / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D013956:Antithyroid Agents; D000939:Epitopes; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011974:Receptors, LH; D011989:Receptors, Thyrotropin