Molecular biological analysis for patheogenesis of Insulin Autoimmune Syndrome

胰岛素自身免疫综合征发病机制的分子生物学分析

• 批准号: 06454251
• 负责人: UCHIGATA Yasuko
• 金额: $ 4.29万
• 依托单位: TOKYO WOMEN'S MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454251/
• 关键词: Insulin autoantibody; HLA; HLA-DRB1^<**>0406; Scatchard analysis; Polyclonal autoantibody; monoclonal autoantibody; T cell receptor; Mixed Lymphocyte Reaction; Scatchrd解析; Mixed lymphocyte reaction

There have been 212 reported cases of insulin autoimmune syndrome (IAS) during the past 20 years in Japan, compared with only about 20 cases in Caucasians since Hirata et al, first described the disease in 1970. The following headings were what we found from the serial studies of IAS in the couples of years.1) Insulin autoantibodies in the insulin autoimmune syndrome were divided into polyclonal and monoclonal ; the incidence of polyclonal responders was relatively high among East Asians, whereas the monoclonal responders were more prevalent in Caucasians.2) Glutamate at position 74 in the HLA-DRB1-chain was presumed to be essential to the production of polyclonal insulin autoantibodies in IAS,whereas alanine at the same position of the HLA-DRB1-chain might be important in the production of monoclonal insulin autoantibodies.3) From the findings described above, T cell reccptor Vbeta usage was investigated in order to know whether the usage was uniform or not and whether the T cell had a restricted CDR3 region on not. So for, the insulin-reacted T cell receptor had a dominant Vbeta8 usage.

在过去的20年中，日本报告了212例胰岛素自身免疫综合征（IAS）病例，而自1970年Hirata等人首次描述该疾病以来，白种人中只有约20例。通过对近年来IAS的系列研究发现：1）胰岛素自身免疫综合征中的胰岛素自身抗体分为多克隆抗体和单克隆抗体;多克隆应答者的发生率在东亚人中相对较高，而单克隆应答者在高加索人中更普遍。2）HLA-DRB 1 - 1中第74位的谷氨酸推测HLA-DRB 1链对IAS中多克隆胰岛素自身抗体的产生是必需的，而HLA-DRB 1链相同位置上的丙氨酸可能对单克隆胰岛素自身抗体的产生是重要的。3）从上述发现，研究了T细胞受体Vbeta的使用，以了解使用是否均匀以及T细胞是否具有限制性CDR 3区。因此，胰岛素反应的T细胞受体主要使用Vbeta 8。

项目成果

山田 ひとみ,内潟 安子ら: "グルタミン免役脱炭酸酵素(GAD)抗体とヒトインスリン自己抗体(IAA)のIDDM発症年齢別陽性率" ホルモンと臨床. 43. 53-56 (1995)

Hitomi Yamada、Yasuko Uchigata 等人：“根据 IDDM 发病年龄的谷氨酰胺免疫脱羧酶 (GAD) 抗体和人胰岛素自身抗体 (IAA) 阳性率”《激素与临床研究》43. 53-56 (1995)。

Uchigata Y, et al.: "Diabetes 1994(Excerpta Medica)" HGlu inHLA-DR4B1 chain isanessential aminoacid residue for polydonal insulin autoantibody production in insulin autoimmune syndrome., 1105-1112 (1995)

Uchigata Y, et al.:“Diabetes 1994(Excerpta Medica)”HLA-DR4B1链中的HGlu是胰岛素自身免疫综合征中多聚胰岛素自身抗体产生的必需氨基酸残基。，1105-1112(1995)

Uchigata Y.: "A novel concept of type VII hypersensitivity induced by insulin autoimmune syndrome (Hirata's disease)" Autoimmunity. 44. 207-208 (1995)

Uchigata Y.：“胰岛素自身免疫综合征（平田病）诱导的 VII 型超敏反应的新概念”自身免疫。

内潟安子: "抗グルタミン酸脱炭素酵素抗体" 感染、炎症、免疫. 26. 60-64 (1996)

Yasuko Uchigata：“抗谷氨酸脱羧酶抗体”感染、炎症、免疫。26. 60-64 (1996)。

Uchigata Y.: "Insulin autoimmune syndrome (Hirata Disease) : clinical features and epidemiology in Japan" Diabetes Research and Clinical Practice. 24. 89-94 (1994)

Uchigata Y.：“胰岛素自身免疫综合征（平田病）：日本的临床特征和流行病学”糖尿病研究和临床实践。