한국인 성인에서 발생하는 인슐린 의존형 당뇨병의 임상 및 면역유전학적 특성

Abstract

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease occurring among genetically susceptible individuals. Although the HLA class II genes and immunological abnormalities are clearly associated with IDDM in all racial groups, there are considerable variations in associated genotypes and prevalence of autoantibodies. Especially, it seems that adult-onset IDDM is somewhat different from childhood- onset IDDM in clinical and immunogenetic aspect. In order to determine the characteristics of the immunogenetic patterns and to use these results as an early diagnostic tool and a guideline of the therapeutic plan in Korean adult- onset IDDM, we investigated the clinical and immunogenetic characteristics in adult-onset IDDM patients. Methods : We investigated the clinical and biochemical characteristics, and measured anti-GAD antibody by immunoradiometric assay or immunoprecipitation after in vitro translation of human GAD cDNA and IA-2 antibody by immunoprecipitaion after in vitro translation of human IA-2cDNA. The distribution of HLA-DR serotypes by lymphocyte microcytotoxicity method, HLA-DQA1 genotypes by restriction fragment length polymorphism and HLA-DQB1 genotypes by dot-blotting analysis using sequence specific oligonucleotide probe were analysed in 233 IDDM patients and controls. Results : 1) Adult-onset patients had more preserved beta cell functions and slowly evolving form of clinical pattern rather than childhood-onset cases. 2) Each prevalences of anti-GAD and IA-2 antibody were 64% and 14.4% in adult-onset patients. Among them, the group with DR9-DQ9 had higher prevalence of antiGAD antibody rather than DR4-DQ4 group. 3) There were increased frequencies of HLA-DR4 and -DR9 in adult-onset patients. Considering the frequency of HLA-DQA1 and -DQB1 and the distribution of DQ heterodimers, they had no significantly increased genotypes or haplotypes. But childhood-onset cases had high frequencies in HLA DR3, -DR4, -DR9 serotypes and DQA1*0301, DQA1*0501, DQB1*0201 genotypes. Conclusion : Korean adult-onset IDDM patients have relatively higher prevalence of anti-GAD antibody implicating autoimmune pathogenesis. HLA genetic markers in adult-onset IDDM were somewhat different from those in childhood-onset cases. This pathogenetic heterogenesity according to age of onset may be due to the influences of other genetic markers and environmental factors involved in the etiology of Korean IDDM.