TSH Receptor Antibody Heterogeneity in Graves' Disease

格雷夫斯病中 TSH 受体抗体异质性

• 批准号: 7158116
• 负责人: Jessica R Smith
• 金额: $ 5.59万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158116
• 关键词: Graves disease; adolescence (12-20); antibody titering; autoantibody; child (0-11); clinical research; diagnosis design /evaluation; dosage; drug adverse effect; enzyme linked immunosorbent assay; epitope mapping; gene expression profiling; hormone receptor; hormone regulation /control mechanism; human subject; longitudinal human study; microarray technology; monoclonal antibody; pathologic process; patient care management; patient oriented research; pharmacogenetics; postdoctoral investigator; prognosis; remission /regression; thyroid function; thyrotropin

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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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

描述（由申请人提供）：Graves疾病是儿童甲状腺功能亢进症的最常见形式，是由模仿TSH作用的甲状腺激素（TSH）受体抗体（TSH）受体抗体（TH）引起的。由于持续免疫减轻所需的抗甲状腺药物的长期病程，这种疾病导致儿童的发病率很高，并且在撤离药物时会出现高复发风险。预测哪些患者最有可能失败的医疗管理能力将大大改善治疗的选择。过去，较大的甲状腺肿大小，诊断年龄，生化严重程度增加和体重指数降低都与预后较差有关，但是这些临床指标缺乏敏感性和特异性。初步数据表明，新的TRAB分析既敏感又特定，以测量坟墓疾病儿童中的Trabs。此外，随着时间的推移，这些抗体的变化在所有患者中均不相同。该提案的目的是前瞻性地跟随患有新诊断为Graves疾病的儿童，并使用微阵列技术来确定是否存在对医疗疗法反应的患者表达的基因，而患者与那些早些时候需要更明确的治疗的患者相对于他们的疾病。