TSH Receptor Antibody Heterogeneity in Graves' Disease

描述（由申请人提供）：Graves病是儿童甲状腺功能亢进最常见的形式，是由促甲状腺素（TSH）受体抗体（TRAbs）引起的，该抗体模拟TSH的作用。由于持续免疫缓解通常需要延长抗甲状腺药物疗程，以及停药后复发的高风险，该病在儿童中导致显著发病率。能够预测哪些病人最有可能失败的医疗管理将大大改善治疗的选择。以往，甲状腺肿大、诊断年龄、生化严重程度增高、体重指数下降均与预后较差相关，但这些临床指标缺乏敏感性和特异性。初步数据表明，新的TRAb检测方法对Graves病儿童的TRAb检测具有敏感性和特异性。此外，这些抗体随时间的变化在所有患者中并不相同。这项提议的目标是前瞻性地跟踪新诊断的格雷夫斯病的儿童，并使用微阵列技术来确定在对药物治疗有反应的患者与那些在疾病早期需要更明确治疗的患者中是否存在表达不同的基因。

DESCRIPTION (provided by applicant): Graves' disease, the most common form of hyperthyroidism in children, is caused by Thyrotropin (TSH) Receptor Antibodies (TRAbs) that mimic the action of TSH. The disease leads to significant morbidity in children both due to the prolonged course of antithyroid medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn. The ability to predict which patients are most likely to fail medical management would greatly improve the choice of therapy. In the past, large goiter size, age at diagnosis, increased biochemical severity, and decreased body mass index have all been associated with a poorer prognosis, but these clinical indicators lack sensitivity and specificity. Preliminary data suggest that the new TRAb assays are both sensitive and specific for the measurement of TRAbs in children with Graves' disease. In addition, variation in these antibodies over time is not the same in all patients. The goal of this proposal will be to prospectively follow children with newly diagnosed Graves' disease and use microarray technology to determine if there are genes whose expression differ in patients who respond to medical therapy versus those who will need more definitive therapy earlier in their disease.