Analysis of TSH receptor antibody and studies of effects of it upon thyroid development and function.

1. 我们从NIH Kohn博士处获得大鼠甲状腺FRTL-5细胞，利用FRTL-5细胞建立了检测tsh受体抗体活性的方法，即tsh结合抑制剂免疫球蛋白（TBII）、促甲状腺抗体（TSAb）、促甲状腺阻断抗体（TSBAb）、抑制碘转运或胸腺苷掺入FRTL-5细胞的抗体。我们在各种自身免疫性甲状腺疾病患者中测定了这些活动，以找出疾病的病因学意义。1)慢性甲状腺炎：儿童期发病的萎缩性自身免疫性甲状腺炎（AAT）患者未检测到tsh受体阻断抗体（TBII和TSBAB），提示儿童期与青春期后发病的AAT发病机制不同。众所周知，携带tsh受体阻断抗体的母亲所生的婴儿甲状腺功能低下，但母亲的tsh受体阻断抗体活性与后代甲状腺功能低下之间的关系尚未完全阐明。我们建立了用正常混合血清稀释母亲血清来预测新生儿甲状腺功能障碍的方法，获得标记TSH与其受体结合50%的抑制，使我们能够产前诊断甲状腺功能减退并超早开始治疗。2) Graves病：诊断时均检测到TBII和TSAB抗体活性，抗甲状腺治疗降低了TBII和TSAB抗体活性。我们对这些活动进行了评估。是否可能是graves病长期预后的良好指标，并发现TSAB是疾病缓解或复发的最有用指标。为了阐明母亲tsh受体抗体活性与子代甲状腺功能障碍的关系，我们研究了母亲血清中tsh和TSAB的活性。我们发现TBII和TSAB活性与新生儿甲状腺毒症的发生有关，而另一方面，在我们提出的一种新的甲状腺功能障碍——短暂性甲状腺功能低下血症的母亲中检测到非常弱的TSAB活性，而与TBII无关。3)克汀病：据报道，生下散发性克汀病的母亲存在一些自身抗体。我们用FRTL-5细胞检测了tsh受体阻断抗体和抑制碘转运或胸腺苷掺入DNA的抗体，但没有发现与正常对照有任何差异。新生儿先天性甲状腺功能减退症筛查：我们开展先天性甲状腺功能减退筛查已有十多年的历史。在全国范围内进行的一项智力发展研究发现，正常对照组和6岁以上的痴呆患者之间存在显著差异。有必要继续进行未来的评估和改进治疗。我们在北海道开展了以人群为基础的克汀病研究，报告了发病率和疾病类型。我们还评估了产前碘代谢，以提高筛查的敏感性和准确性。少

1. We were distributed rat thyroid FRTL-5 cell from Dr. Kohn of NIH and using FRTL-5 cell , we have established the methods for detection of TSH-receptor antibody activities, that is, TSH-binding inhibitor immunoglobulins(TBII),Thyroid-stimulating antibody(TSAb),Thyroid-stimulation blocking antibody(TSBAb),antibody which inhibit iodine transport or thysidine incorporation into FRTL"5 cells. We have determined these activities in patients with various auto-immune thyroid diseases to find out any etiological significance of the diseases.1) Chronic thyroiditis: We couldn't detected TSH-receptor blocking antibodies(TBII and TSBAB) in patients with atrophic autoinsune thyroiditis(AAT) of childhood onset which suggested the pathogenesis of AAT in childhood is different from that of postpubertal onset. It is well known that mother who possessed TSH-receptor blocking antibody give birth hypothyroid infant however,the correlation between mother's TSH-receptor blocking antibody activities and ou … More tcome of their offspring have not fully elucidated. We have established the method to predict thyroid dysfunction of newborn infants with diluting mother's serum with normal pooled serum to obtained 50% inhibition of labeled TSH binding to its receptor which enable us to prenatal diagnosis of hypothyroidism and ultra-early start of treatment.2) Graves' disease: Both TBII and TSAB antibody activity were detected at diagnosis and these activities were decreased with anti-thyroid treatment. We have evaluated these activity.whether it might be a good indicator of long-term prognosis of Grave's disease and found that TSAB is the most useful indicator of remission or relapse of the disease. To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, We have studies TSII and TSAB activities in mother's sera. We found that TBII and TSAB activities were responsible for development neonatal thyrotoxicosis, while on the other hand very weak TSAB activities regardless of TBII were detected in mothers who gave birth infants with transient hypothyroxinemia which is a new thyroid dysfunction proposed by us.3) Cretinism: It was reported that there are some autoantibodies in mothers who gave birth sporadic cretinism. We have evaluated TSH-receptor blocking antibody and antibodies which inhibit iodine transport or thysidine incorporation into DNA using FRTL-5 cell, however, we could not found any difference between normal controls.2. Neonatal screening for congenital hypothyroidism: More than ten years has passed since we start screening for congenital hypothyroidism. Nationwide study of mental development was performed and found there is a significant difference between normal control and cretinism who were over 6 years of age. It is necessary to continue future evaluation and improvement of treatment.We have conducted population-basis study of cretinism in Hokkaido and reported the incidence and types of disease. We also evaluated iodine metabolism in prenatal period to improve sensitivity and accuracy of screening. Less