Graves' & Hashimoto's diseases and apoptosis

格雷夫斯的

• 批准号: 08671175
• 负责人: TAKASU Nobuyuki
• 金额: $ 1.47万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671175/
• 关键词: Grave's disease; Hashimoto's disease; thyrotoxicosis; hypothyroidism; TSH receptor antibody; TRAb; TSAb; ATL; 甲状腺自己免疫疾患; アポトーシス; 成人T細胞白血病; HTLV-I carrier

There are two autoimmune thyroid diseases ; Graves' and Hashimoto's diseases. The former causes thyrotoxicosis and the latter hypothyroidism. There are many patients with Graves' and Hashimoto's diseases. However, the mechanisms for the development of both diseases are still poorly known. Apoptosis might play some roles in the development of Graves' and Hashimoto's diseases.1)Graves' disease TRAb (TSH receptor antibody) causes Graves' disease. This TRAb is thyroid stimulating antibody (TSAb). This TSAb stimulates thyroid glands and increases thyroid hormone synthesis and secretion ; thus TSAb causes thyrotoxicosis. We studied TSAb and TBII (TSH-binding inhibitory IgG) as TRAb in 277 untreated Graves' patients and 686 normal control subjects (Takasu N et al : J Endocrinol Invest 20 : 452-461,1997). ROC analysis revealed that cut-off value for TSAb is 150% and that for TBII is 10%. Almost all untreated Graves' patients have positive TSAb and/or TBII.TSAB and TBII decreased to normal levels with antithyroid drug treatment. The changes of TSAb and TBII predict the clinical courses of Graves' patients.Hashimoto's diseases Lymphocyte abnormality plays an essential role in the development of Hashimoto's thyroiditis. Adult T-cell leukemia (ATL) is a disease of T-lymphocyts. Immune abnormalities are seen in ATL patients. We reported that high prevalence of Hashimoto's thyroiditis in the patients with ATL and HTLV-I carriers (Clin Endocrinol 45 : 461-466,1996).We also revealed the mechanism of the development of blocking antibody-induced hypothyroidism in the patients with atrophic thryoiditis (Clin Endocrinol 47 : 319-324,1997).

有两种自身免疫性甲状腺疾病; Graves病和桥本氏病。前者引起甲状腺毒症，后者引起甲状腺功能减退症。有许多患者患有Graves病和桥本病。然而，这两种疾病的发展机制仍然知之甚少。细胞凋亡可能在Graves病和桥本病的发生发展中起一定作用。1）Graves病TRAb（TSH受体抗体）引起Graves病。这种TRAb是甲状腺刺激抗体（TSAb）。这种TSAb刺激甲状腺并增加甲状腺激素的合成和分泌;因此TSAb引起甲状腺毒症。我们在277名未经治疗的Graves '患者和686名正常对照受试者中研究了TSAb和TBII（TSH结合抑制性IgG）作为TRAb（Takasu N等：J Endocrinol Invest 20：452 - 461，1997）。ROC分析显示，TSAb的截断值为150%，TBII的截断值为10%。几乎所有未经治疗的Graves病患者都有TSAb和/或TBII阳性，抗甲状腺药物治疗后TSAB和TBII降至正常水平。TSAb和TBII的变化可预测Graves病的临床病程。桥本氏病淋巴细胞异常在桥本氏甲状腺炎的发生发展中起重要作用。成人T细胞白血病（ATL）是一种T淋巴细胞疾病。在ATL患者中观察到免疫异常。我们报道了ATL和HTLV-Ⅰ携带者桥本甲状腺炎的高患病率（Clin Endocrinol 45：461 - 466，1996），并揭示了萎缩性甲状腺炎患者发生阻断性抗体诱导的甲状腺功能减退的机制（Clin Endocrinol 47：319 - 324，1997）。

项目成果

Kouki, Takasu et al :"Demonstration of fragments with thyrid stimulating activity from thyroid stimulation blocking antibodies molecules by papain digestion." Clin Endocrinol. 47. 319-324 (1997)

Kouki、Takasu 等人：“通过木瓜蛋白酶消化，展示来自甲状腺刺激阻断抗体分子的具有甲状腺刺激活性的片段。”

Akamine, Takasu et al :"Association of HTLV-I with autoimmune thyroiditis in patients with adult T-cell Leukemia (ATL) and HTLV-I carriers." Clin Endocrinol. 45. 461-466 (1996)

Akamine、Takasu 等人：“成人 T 细胞白血病 (ATL) 和 HTLV-I 携带者患者中 HTLV-I 与自身免疫性甲状腺炎的关联。”

Kouki T,Takasu N et al.: "Demonstration of fragments with thyroid stimulating activity from thyroid stimulation blocking antibodies-IgG molecules by papain digestion" Clin Endocrinology. 47. 319-324 (1997)

Kouki T、Takasu N 等人：“通过木瓜蛋白酶消化，演示来自甲状腺刺激阻断抗体-IgG 分子的具有甲状腺刺激活性的片段”《临床内分泌学》。

Ohshiro K, Takasu N et al.: "Molecuila cloning of rat maerophage-stimulating protein and ito inrolnmenl in the male reprodutive selatem" Biochem Biophxp Res Commun. 227. 273-280 (1996)

Ohshiro K、Takasu N 等人：“大鼠巨噬细胞刺激蛋白和 ito inrolnmenl 在雄性生殖细胞中的分子克隆”Biochem Biophxp Res Commun。

Takasu et al :"Thyroid-stimulating antibody and TSH-binding inhibitory immunoglobulin in 277 Graves'patients and in 686 normal subjects." J Endocr Inv. 20. 526-532 (1997)

Takasu 等人：“277 名格雷夫斯患者和 686 名正常受试者中的甲状腺刺激抗体和 TSH 结合抑制性免疫球蛋白。”