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Immunological studies for prevention and treatment of insulin-dependent diabetes mellitus in childhood

预防和治疗儿童胰岛素依赖型糖尿病的免疫学研究

基本信息

批准号：
62570430
负责人：
MATSUDA Hiroshi
金额：
$ 1.54万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570430/
关键词：
Insulin-dependent diabetes mellitus HLA NOD mice cyclosporin ICSA インスライティスインスライテイス IDDM 免疫療法 BBラット

项目摘要

It is well established that autoimmune mechanisms are involved in the development of insulindependent diabetes mellitus(IDDM) but there are at present no immunological ways to treat IDDM. This study was aimed to elucidate the autoimmune mechanisms in IDDM and search for possible immunotherapies agaist IDDM.IDDM of Japanese was found to be associated with HIA as is IDDM of Caucasians; an autoimmune type of IDDM was associated with HLA-DRw9 and a non-autoimmune type of IDDM with HLA-DR4. ICA was detected with a high frequency in both types of IDDM at the early period although the duration of ICA differed between two types of IDDM. These findings indicate that HLA and ICA are useful to predict the development of IDDM in children who have a family history of IDDM or who are positive for urinary glucose at the screening at school. HLA is particularly useful to find an autoimmune type of IDDM agaist which the applications of immunotherapies might be possible.In order to search for immunotherapies agaist IDDM, cyclosporin and B-1,3 D-glucan were studied in animal models of IDDM, NOD mice and BB rats. These immunosuppressor and immunomodulator were found to suppress the insulitis and overt diabetes of these animals. Furthermore, dietary composition was shown to be involved in the prevention of overt diabetes in NOD mice. These findings suggest that the immunotherapies combined with dietary therapies might be possible ways to prevent or treat IDDM. Further studies on the immunological mechanisms underlying IDDM lead to the development of better immunotherapies agaist IDDM.

胰岛素依赖型糖尿病（IDDM）的发生与自身免疫机制有关，但目前尚无免疫治疗方法。本研究旨在阐明IDDM的自身免疫机制，并寻找可能的IDDM免疫治疗方法。发现日本人的IDDM与HIA相关，白种人的IDDM也与HIA相关；自身免疫性IDDM与HLA-DRw9相关，非自身免疫性IDDM与HLA-DR4相关。两种类型的IDDM在早期都检测到高频率的ICA，尽管ICA的持续时间在两种类型的IDDM之间有所不同。这些发现表明，HLA和ICA对于有IDDM家族史或在学校筛查时尿糖阳性的儿童预测IDDM的发展是有用的。HLA对发现自身免疫性IDDM特别有用，免疫疗法的应用可能是针对这种类型的IDDM。为了寻找抗IDDM的免疫治疗方法，我们在IDDM动物模型、NOD小鼠和BB大鼠中研究了环孢素和b -1,3 -葡聚糖。这些免疫抑制剂和免疫调节剂被发现可以抑制这些动物的胰岛素和显性糖尿病。此外，饮食成分被证明参与预防NOD小鼠的显性糖尿病。这些发现表明，免疫疗法结合饮食疗法可能是预防或治疗IDDM的可能方法。对IDDM免疫机制的进一步研究有助于开发更好的IDDM免疫疗法。