Molecular cell-biological pathogenesis of insnlin autoimmune syndrome

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。

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.