The Karlsburg Type 1 Diabetes Risk Study of a Normal Schoolchild Population: Association of β-Cell Autoantibodies and Human Leukocyte Antigen-DQB1 Alleles in Antibody-Positive Individuals

The intent of this study was to analyze the prevalence of diabetes-associated autoantibodies (AAbs) at or above the 99th percentile as well as their association with human leukocyte antigen (HLA)-DQB1 alleles in a normal population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by 125I-antigen binding and islet cell antibodies (ICA) immunohistochemically in 181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P < 0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001–0.006) as well as a decreased frequency in the protective allele *0602 (P < 0.001–0.022). DQB1*0602 was completely absent within children with multiple AAbs or with GADA, IA2-A, o...