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

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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.