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© 2002 by the American Diabetes Association, Inc.
Genetic Risk Determines the Emergence of Diabetes-Associated Autoantibodies in Young Children
1 Department of Pediatrics, the Juvenile Diabetes Research Foundation Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
2 Department of Virology, the Juvenile Diabetes Research Foundation Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
3 Department of Pediatrics, University of Oulu, Oulu, Finland
4 Department of Pediatrics, University of Tampere Medical School, Tampere, Finland
5 Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Timing of onset of autoimmunity is a prerequisite for unmasking triggers and pathogenesis of type 1 diabetes. We followed 4,590 consecutive newborns with 8 or 3% HLA-DQB1 conferred risk for type 1 diabetes at 3-, 6-, or 12-month intervals up to 5.5 years of age. Islet cell autoantibodies (ICAs) and, in the 137 children with ICAs, insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and IA-2 protein autoantibodies (IA-2As) were measured. Children with high genetic risk developed ICAs more often than those with moderate risk (log-rank P = 0.0015); 85 and 91% remained ICA negative by 5 years of age, respectively. The time of appearance of biochemical autoantibodies was then compared with the appearance of ICAs. IAAs and GADAs emerged usually before ICAs (means -1.8 and -1.5 months, respectively) and IA-2As after ICAs (mean 2.0 months). Ninety-five percent of all IAAs, GADAs, and IA-2As seroconversions occurred in a cluster (-12 to 8 months) around the ICA seroconversion. We conclude that diabetes-associated autoantibodies emerged in children with predisposing HLA-DQB1 alleles after 3 months of age at a constant tempo, determined by the genetic risk level, usually in the order of IAA, GADA, ICA, and IA-2A. Seroconversion to multiple autoantibody positivity usually occurred tightly clustered in time.
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