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Development of Mass-Screening Method for the Identification of Patients at Risk of Developing Type 1 Diabetes Mellitus.

开发用于识别有患 1 型糖尿病风险的患者的大规模筛查方法。

基本信息

批准号：
11672315
负责人：
KOHNO Takeyuki
金额：
$ 2.24万
依托单位：
Setsunan University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672315/
关键词：
Type 1 Diabetes Mellitus Albumin IgA Mucosal Immunity Enzyme Immunoassay Cytokines

项目摘要

The study on the development of mass-screening method for the identification of patients at risk of developing type 1 diabetes mellitus (DM) is described. The results are as follows.1. An ultrasensitive enzyme immunoassay (immune-complex transfer enzyme immunoassay) for IgA antibodies to cow's milk proteins has been developed, and the antibody levels in sera from patients with DM and healthy subjects were compared. However, no significant difference was observed. If anti-idiotype antibodies to the antibodies were present in serum, they might interfere with the assay, so suitable ELISA format was employed to minimize such interference. As results, the levels of IgA antibodies not only to the cow's milk proteins but also to an other food protein were significantly higher in former than latter.2. 50% of the patients had DQB1^*0401-DRB1^*0405 haplotype. In the patients with the haplotype, the levels of IgA antibodies to the cow's milk proteins, IgA and TGF-beta were significantly higher than those in the other patients. This was suggested that, in the digestive tract, an antigen presentation to Th3 was accelerated by the haplotype, subsequently, TGF-beta production was elevated, consequently, IgA antibody production was enhanced. Therefore, the IgA antibody response, that is, mucosal immune response, to the food antigen become a reliable marker for identification of patients at risk of developing DM.3. The assay method to assess the mucosal immune response to the cow's milk proteins using dried urine samples has been developed and validated. In addition, the levels of IgA antibodies in the dried urine samples and serum samples were correlated.In conclusion, the mass-screening method, in which the mucosal immune response to the cow's milk proteins is assessed by using the dried urine, can provide us with a reliable method for identification of patients at risk of developing DM.

本文介绍了一种鉴别1型糖尿病（DM）高危患者的大规模筛查方法的研究进展。结果如下：1。建立了一种针对牛奶蛋白的IgA抗体的超灵敏酶免疫测定法（免疫复合物转移酶免疫测定法），并比较了糖尿病患者和健康人血清中的抗体水平。然而，没有观察到显著差异。如果血清中存在针对抗体的抗独特型抗体，则可能干扰检测，因此采用合适的ELISA格式来减少这种干扰。结果表明，不仅针对牛奶蛋白的IgA抗体水平，而且针对其他一种食物蛋白的IgA抗体水平，前者明显高于后者。50%的患者为DQB1^*0401-DRB1^*0405单倍型。在单倍型患者中，针对牛奶蛋白、IgA和tgf - β的IgA抗体水平明显高于其他患者。这表明，在消化道中，单倍型加速了抗原向Th3的递呈，随后，tgf - β的产生升高，从而增强了IgA抗体的产生。因此，IgA抗体反应，即粘膜对食物抗原的免疫反应，成为鉴别患dm风险患者的可靠标志。已经开发并验证了使用干燥尿液样本评估粘膜对牛奶蛋白免疫反应的测定方法。此外，干燥尿液样本和血清样本中的IgA抗体水平存在相关性。综上所述，通过干燥的尿液来评估粘膜对牛奶蛋白的免疫反应的大规模筛查方法，可以为我们提供一种可靠的方法来识别有发展为糖尿病风险的患者。