UTILITY OF ASSESSING TSH RECEPTOR ANTIBODY IN GRAVES' DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项提议的目标将是： 1)前瞻性跟踪一组新诊断为Graves病的儿童和青少年 2)在诊断时、6个月和12个月检测甲状腺功能(T4、游离T4、总T3和TSH)、TSH受体抗体(通过ELISA法和生物测定法)和TSH受体抗体的寡克隆性(用lambda/kappa比率评估 3)确定甲亢的初始严重程度(由临床和激素参数决定)是否与初始TSH受体抗体效价和/或寡克隆或两者有关 4)确定TSH受体抗体在6个月和12个月时的滴度是否与： A)甲亢的初始严重程度(由临床和激素参数决定) B)初始TSH受体抗体效价(通过酶联免疫吸附试验和生物测定) C)最初的TSH受体抗体寡克隆，以及6个月和12个月时的TSH受体抗体寡克隆 5)分析患者确诊时、6个月和12个月TSH受体抗体异质性的病程； 我们假设： 1)在Graves病的儿童中，75%的TSH受体抗体是多克隆的，用lambda/kappa比率进行评估，25%的儿童将有寡克隆抗体 2)寡克隆抗体的效力更强，受影响的患者病情更严重，缓解的可能性更小 3)确诊时病情最严重的患者TSH受体抗体滴度最高，缓解药物治疗的可能性较小 4)25%的患者的克隆性会随着疾病的进展而改变。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of this proposal will be to: 1) Prospectively follow a group of children and adolescents with newly diagnosed Graves' disease 2) Measure thyroid function tests (T4, Free T4, Total T3, and TSH), TSH receptor antibodies (by both ELISA and bioassay), and TSH receptor antibody oligoclonality (as assessed by lambda/kappa ratio) at diagnosis, 6 months, and 12 months 3) Determine whether initial severity of hyperthyroidism (as determined by both clinical and hormonal parameters) is related to initial TSH receptor Ab potency and/or oligoclonality or both 4) Determine whether TSH receptor Ab titer at 6 months and at 12 months is related to: a) initial severity of hyperthyroidism (as determined by both clinical and hormonal parameters) b) initial TSH receptor Ab potency (by both ELISA and bioassay) c) initial TSH receptor Ab oligoclonality, as well as TSH receptor Ab oligoclonality at 6 months and 12 months 5) Characterize the course of TSH receptor Ab heterogeneity at diagnosis, 6 months and 12 months in individual patients; We hypothesize that: 1) Amongst children with Graves' disease, 75% will have TSH receptor Abs that are polyclonal as assessed by lambda/kappa ratio and 25% will have oligoclonal Abs 2) Oligoclonal Abs are more potent and affected patients have more severe disease and are less likely to remit 3) Those patients who have the most severe disease at diagnosis will have the highest TSH receptor Ab titers and will be less likely to remit on medical therapy 4) 25% of patients will have a change in clonality with disease progression.