Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Graves' patients treated with antithyroid drugs.
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.
Kim
Tae Yong
TY
Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
Park
Young Joo
YJ
Park
Do Joon
DJ
Chung
Hyun-Kyung
HK
Kim
Won Bae
WB
Kohn
Leonard D
LD
Cho
Bo Youn
BY
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
D013956:Antithyroid Agents; D000939:Epitopes; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011974:Receptors, LH; D011989:Receptors, Thyrotropin