Islet autoantibodies precede the clinical onset of Type I (insulin-dependent) diabetes mellitus.
The cumulative development of such autoantibodies in infants followed from birth and in particular infants with high-risk HLA genotypes is poorly defined, but such information is essential to design trials to prevent islet autoimmunity.
HLA genotypes were determined in offspring of parents with Type I diabetes who were followed from birth for at least 2 years (median follow-up : 3.1 years) and who were characterised for the expression of insulin, GAD65, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of age.
The HLA genotypes DRB1*03/04 (DQB1 *57non-Asp) and DRB1*04/04 (DQB1*57non-Asp) were present in 7. 1% and 5.0% of offspring of parents with Type I diabetes.
The frequency of both genotypes was increased in offspring who developed islet autoantibodies within the first 2 years of life (27.3% vs 5.5%, odds ratio 6.3 [p=0.002] and 22.7% vs 4.2%, odds ratio 6.6 [p=0.003]) and half of all offspring who developed antibodies had these genotypes.
Other genotypes were not associated with an increase in risk.
By life-table analysis, the cumulative risk of developing islet autoantibodies by the age of 2 years was 20% (95% CI 9.4,30.6) for offspring carrying either the DRB1*03/04 (DQB1 *57non-Asp) or the DRB1*04/04 (DQB1*57non-Asp) genotype compared with 2.7% (95% CI 1.2,4.2) for offspring without these genotypes (p<0.0001). (...)
Mots-clés Pascal : Ilot Langerhans, Autoanticorps, Système HLA, Génotype, Autoimmunité, Facteur risque, Diabète insulinodépendant, Pancréas endocrine, Endocrinopathie, Immunopathologie, Maladie autoimmune, Enfant, Homme, Prévention, Epidémiologie, Allemagne, Europe
Mots-clés Pascal anglais : Langerhans islet, Autoantibody, HLA-System, Genotype, Autoimmunity, Risk factor, Insulin dependent diabetes, Endocrine pancreas, Endocrinopathy, Immunopathology, Autoimmune disease, Child, Human, Prevention, Epidemiology, Germany, Europe
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0327693
Code Inist : 002B21E01A. Création : 16/11/1999.