title: Patterns of β-cell autoantibody appearance and genetic associations during the first years of life.
abstract: We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D), the pattern of autoantibody appearance was analyzed in 520 children with advanced β-cell autoimmunity associated with high risk for disease. In 315 cases, a single biochemical autoantibody could be identified in the first positive sample as insulin (insulin autoantibody [IAA]) in 180, as GAD (GAD antibody [GADA]) in 107, and as IA-2 antigen (IA-2 antibody [IA-2A]) in 28. The age at seroconversion differed significantly between the three groups (P = 0.003). IAA as the first autoantibody showed a peak time of appearance during the second year of life, whereas GADA as the first autoantibody peaked later, between 3 and 5 years of age. The risk-associated insulin gene rs689 A/A genotypes were more frequent in children with IAA as the first autoantibody compared with the other children (P = 0.002). The primary autoantigen in the development of β-cell autoimmunity and T1D seems to strongly correlate with age and genetic factors, indicating heterogeneity in the initiation of the disease process.
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Anna
authors.initials: A
authors.lastname: Hammais
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Laine
authors.forename: Johanna
authors.initials: J
authors.lastname: Lempainen
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000235:genetics*; D015551:Autoimmunity; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007330:Insulin Antibodies / Q000097:blood* / Q000235:genetics*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D007330:Insulin Antibodies