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

TSH受体抗体分析及其对甲状腺发育和功能的影响研究。

• 批准号: 62480223
• 负责人: MATSUURA Nobuo
• 金额: $ 3.01万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480223/
• 关键词: TSH-receptor antibody; TSH-binding inhibitor immunoglobulin(TBII); Thyroid stimulating antibody (TSAb); Thyroid-stimulation blocking antibody(TSBAb); Cretinism; Graves' disease; Atrophic autoimmune thyroiditis(AAT); Goitrous autoimmune thyroiditis(

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

1.我们从NIH的Kohn博士处获得大鼠甲状腺FRTL-5细胞，并利用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）、甲状腺刺激抗体（TSAb）、甲状腺刺激阻断抗体（TSBAb）、抑制碘转运或胸腺嘧啶掺入FRTL-5细胞的抗体。我们已经确定了各种自身免疫性甲状腺疾病患者的这些活动，以找出这些疾病的病因学意义。1）慢性甲状腺炎：我们在儿童期发病的萎缩性自身免疫性甲状腺炎（AAT）患者中未检测到TSH受体阻断抗体（TBII和TSBAB），这表明儿童期AAT的发病机制与青春期后发病的不同。TSH受体阻断抗体阳性的母亲产下甲减儿是众所周知的，然而，母亲TSH受体阻断抗体活性与甲减儿的出生率之间的相关性尚不清楚。 ...更多信息 他们的子孙后代都没有完全阐明。我们已经建立了一种方法来预测新生儿甲状腺功能不全的稀释母亲的血清与正常混合血清，以获得50%的抑制标记TSH结合其受体，使我们能够产前诊断甲状腺功能减退症和超早期开始治疗。2）Graves病：TBII和TSAB抗体活性检测在诊断和抗甲状腺治疗这些活动减少。我们已经评估了这些活性是否可能是格雷夫斯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异常的关系，我们研究了母亲血清中TSII和TSAB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，而在我们提出的一种新的甲状腺功能障碍--一过性低甲状腺素血症的母亲中检测到非常弱的TSAB活性（不考虑TBII）。3）克汀病：据报道，在分娩散发性克汀病的母亲中存在一些自身抗体。我们用FRTL-5细胞评价了TSH受体阻断抗体和抑制碘转运或胸腺嘧啶核苷掺入DNA的抗体，但与正常对照组之间没有发现任何差异.先天性甲状腺功能减退症的新生儿筛查：自我们开始筛查先天性甲状腺功能减退症以来，已经过去了十多年。对全国6岁以上的克汀病儿童进行了智力发育的调查，发现正常对照组与克汀病儿童智力发育有显著性差异。我们在北海道进行了以人群为基础的克汀病研究，并报告了发病率和疾病类型。同时对产前碘代谢进行评价，以提高筛查的敏感性和准确性。少

项目成果

Nobuo Matsubara: "The prediction of thyroid function in infants born to mothers with chronic thyroiditis." Endocrinologia,Japonica. 36. 865-871 (1989)

Nobuo Matsubara：“患有慢性甲状腺炎的母亲所生婴儿的甲状腺功能预测。”

Nobuo Matsubara: "Comparison of atrophic and goitrous autoimmune thyroiditis in children:Clinical,laboratory and TSH-receptor antibody studies." Europian J.of Pediatrics accepted for publication.

Nobuo Matsubara：“儿童萎缩性和甲状腺肿自身免疫性甲状腺炎的比较：临床、实验室和 TSH 受体抗体研究。”

Nobuo Matsubara: "TSH-receptor antibodies in mothers with autommnune thyroid disease and outcome in their offspring.in Progress in Thyroidology 1989.M Lee,C-S Koh,J Eastman,S Nagataki edited" Korea Medical Publishing Company, p123-126 (1989)

Nobuo Matsubara：“患有自身免疫性甲状腺疾病的母亲中的 TSH 受体抗体及其后代的结果。甲状腺学进展 1989 年。M Lee、C-S Koh、J Eastman、S Nagataki 编辑”韩国医学出版公司，第 123-126 页（1989 年）

Nobuo Matsubara: "TSH-receptor antibodies in mothers with autommune thyroid disease and outcome in their offspring.Endocrine Chronobiology,edited by Tsutomu Hiroshige." Hokkaido University Press, (1990)

Nobuo Matsubara：“患有自身免疫性甲状腺疾病的母亲中的 TSH 受体抗体及其后代的结果。内分泌时间生物学，由 Tsutomu Hiroshige 编辑。”

Fukushi M: "Measurements of free thyroxine and free triiodothyronine in dried blood on filter paper and its application to neonatal thyroid screening." J Jpn Pediatr Soci 91:5-11, 1987.

Fukushi M：“滤纸上干燥血液中游离甲状腺素和游离三碘甲状腺原氨酸的测量及其在新生儿甲状腺筛查中的应用。”