Molecular cell-biological pathogenesis of insnlin autoimmune syndrome

胰岛素自身免疫综合征的分子细胞生物学发病机制

• 批准号: 10670432
• 负责人: UCHIGATA Yasuko
• 金额: $ 2.05万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670432/
• 关键词: Insulin Autoimmune Syndrome; Insulin autoantibody; clonality; DR4 allele; HnArestriction; クロナーリテイ; DRアリール; HLA; T細胞レセプター

Insulin autoimmune syndrome (IAS) is a syndrome characterized by hypoglycemia, especially in fasting which was first reported by Hirata (JnJpn Diabetes SOC 13 : 312,1970). Insulinautoantibies has 2 clonalities which is polyclonal and monoclonal. Both of them have high-capacity and low-affinity binding constant which are determined by Scatchiard analysis using human insulin.Since reported by Hirata in 1970, we collected 244 patient record with insulin autoimmune syndrome in Japan until 1997. A half of them was treated with sulfhydroxy compounds such as Thiola and Tathione. Approximately 9 people are supposed to develop IAS per year.Insulin-reactive T cell receptors had a high frequent usage of Vβ6,8, and 20. Moreover, they were Th T lymphocytes.There are very rare syndrome in Caucasians. However, there are some Caucasian patients with IAS.We diagnosed 2 Portuguese patient and 1 Argentina patient with IAS.One of Portuguese patients had polyclonal Insulin autoantiby with DRB1^*0406/^* 1302, and the other had monoclonal insulin autoantibdy wi DRB1^*0403/0701. The Argentina patient with IAS had monoclonal insulin autoantibody with DRB1^*0401/0403. The results suppots our hypothesis that polyclonal insulin antibody production in IAS is ristricted with DRB1^*0406 and monoclonal antibody production ia related with the DRB1 allele except DRB1^*0406.

胰岛素自身免疫综合征（insulin autoimmune syndrome，IAS）是由Hirata（日本糖尿病SOC 13：312，1970）首次报道的以低血糖，尤其是空腹时低血糖为特征的综合征。胰岛素自身抗体有多克隆和单克隆两种。自1970年Hirata报道以来，我们收集了日本244例胰岛素自身免疫综合征患者的病历，直到1997年，我们收集了244例胰岛素自身免疫综合征患者的病历。其中一半用巯基化合物如硫代巴比妥和硫代巴比妥处理。每年约有9人发生IAS，胰岛素反应性T细胞受体中Vβ 6、8和20的使用频率较高。在白种人中，这种综合征非常罕见。我们诊断了2例葡萄牙患者和1例阿根廷患者，其中1例葡萄牙患者的多克隆胰岛素自身抗体为DRB 1 ^*0406/^* 1302，另1例患者的单克隆胰岛素自身抗体为DRB 1 ^*0403/0701。阿根廷IAS患者的单克隆胰岛素自身抗体为DRB 1 ^*0401/0403。结果支持了我们的假设，即IAS中多克隆抗体的产生受DRB 1 ^*0406的限制，而单克隆抗体的产生除DRB 1 ^*0406外与DRB 1等位基因有关。

项目成果

Uchigata Y Hirata Y.: "Insulin autoimmune syndrome (IAS, Hirata disease)"Ann Med Interna. 150. 245-253 (1999)

Uchigata Y Hirata Y.：“胰岛素自身免疫综合征（IAS，平田病）”Ann Med Interna。

Uchigata Y.Hirata Y.: "Insulin autoimmune syndrome (IAS, Hirata disease)"Endocrine and Organ Specific Autoimmunity (R.G.Landes, USA). 135-148 (1999)

Uchigata Y.Hirata Y.：“胰岛素自身免疫综合征（IAS，平田病）”内分泌和器官特异性自身免疫（R.G.Landes，美国）。

Uchigata Y, Hirata Y, Omori Y, Iwamoto Y, Tokunaga K.: "Worldwide differences in incidence of insulin autoimmune syndrome (IAS, Hirata disease) with respect to the evolusion of HLA-DR4 alleles"Human Immunology. 61. 154-157 (2000)

Uchigata Y、Hirata Y、Omori Y、Iwamoto Y、Tokunaga K.：“与 HLA-DR4 等位基因的进化有关的胰岛素自身免疫综合征（IAS、平田病）发病率的全球差异”人类免疫学。

Y.Uchigata,Y.Hirata: "Endocrine and Organ Specific Autoimmunity Chap 7. Insulin Autoimmune Syndrome"R.G.Landes (TX.USA). 271 (1999)

Y.Uchigata、Y.Hirata：“内分泌和器官特异性自身免疫第 7 章。胰岛素自身免疫综合征”R.G.Landes (TX.USA)。

Y.Uchigata,Y.Hirata: "Endocrine and Organ Specific Autoimmunity Chap 7.Insulin Autoimmune Syndrome"R.G.Landes (TX.USA). 271 (1999)

Y.Uchigata、Y.Hirata：“内分泌和器官特异性自身免疫第 7 章。胰岛素自身免疫综合征”R.G.Landes（德克萨斯州美国）。