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症的最常见形式，由模拟促甲状腺激素（TSH）作用的促甲状腺激素（TSH）受体抗体（TRAb）引起。这种疾病导致儿童发病率很高，这是由于持续免疫缓解通常需要抗甲状腺药物治疗的疗程延长，以及停药后复发的风险很高。预测哪些患者最有可能失败的医疗管理的能力将大大改善治疗的选择。在过去，甲状腺肿体积大，诊断时年龄大，生化严重程度增加，体重指数降低都与预后较差有关，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检测试剂盒对Graves病儿童TRAb的测量既敏感又特异。此外，这些抗体随时间的变化在所有患者中并不相同。这项提案的目标是前瞻性地跟踪新诊断的Graves病儿童，并使用微阵列技术来确定是否有基因的表达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存在差异。

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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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.