AUTOIMMUNE AND CLINICAL CHARACTERISTICS OF TYPE-I DIABETES IN CHILDREN WITH DIFFERENT GENETIC RISK LOADS DEFINED BY HLA-DQB1 ALLELES

1. The impact of different genetic risk loads defined by HLA-DQB1 alle les on the autoimmune and clinical characteristics of 647 children and adolescents with recent-onset Type I diabetes was evaluated in a pros pective population-based study. The subjects were divided into four gr oups based on HLA-DQB1 genotypes: DQB10302/0201 (high risk), *0302/x (moderate risk), 0201/y (low risk) and *z/z (decreased risk). 2, Clos e to two thirds (62.3%) of the subjects possessed a high or moderate r isk genotype. A decreased frequency of positivity for islet cell antib odies OCA) and insulin autoantibodies (IAA) (76.8% compared with 85.3% ; P = 0.05, and 30.5% compared with 50.8%, P = 0.0006, respectively) b ut not of positivity for antibodies to the 65 kDa isoform of glutamate decarboxylase was observed in children with the DQB10201/y genotype compared with other children. Among ICA-negative subjects, those with the DQB10201/y genotype had higher serum C-peptide levels over the fi rst 2 years after the diagnosis of Type I diabetes than those with oth er genotypes (P = 0.028). 3, Our data provide some evidence of HLA-DQB 1-determined heterogeneity in the autoimmune and clinical characterist ics of childhood Type I diabetes at the time of the clinical manifesta tion. This suggests differences between children with various HLA-DQB1 genotypes in the pace and/or intensity of the beta-cell destructive p rocess leading to clinical Type I diabetes.