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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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(申请人提供)：Graves病是儿童中最常见的甲亢形式，由促甲状腺激素(TSH)受体抗体(TRABS)模拟TSH的作用而引起。这种疾病导致儿童发病率很高，这既是因为持续的免疫缓解通常需要较长的抗甲状腺药物疗程，也是因为停药后复发的风险很高。能够预测哪些患者最有可能无法通过医疗管理，这将极大地改善治疗选择。在过去，甲状腺肿大、确诊时的年龄、生化严重程度的增加和体重指数的下降都与较差的预后有关，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检测方法对Graves病儿童的TRAb检测既敏感又特异。此外，这些抗体随时间的变化在所有患者中并不相同。这项提议的目标将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在对药物治疗有反应的患者中，与那些需要在疾病早期进行更明确治疗的患者相比，是否存在基因表达不同的情况。