Molecular biological analysis for patheogenesis of Insulin Autoimmune Syndrome

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。

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.