Patterns of β-Cell Autoantibody Appearance and Genetic Associations During the First Years of Life
- Jorma Ilonen1,2⇑,
- Anna Hammais1,
- Antti-Pekka Laine1,
- Johanna Lempainen1,3,4,
- Outi Vaarala5,
- Riitta Veijola6,7,
- Olli Simell3,4 and
- Mikael Knip8,9,10,11
- 1Immunogenetics Laboratory, University of Turku, Turku, Finland
- 2Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland
- 3Department of Pediatrics, University of Turku, Turku, Finland
- 4Turku University Hospital, Turku, Finland
- 5Immune Response Unit, National Institute for Health and Welfare, Helsinki, Finland
- 6Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
- 7Oulu University Hospital, Oulu, Finland
- 8Children’s Hospital, University of Helsinki, Helsinki, Finland
- 9Helsinki University Hospital, Helsinki, Finland
- 10Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 11Folkhälsan Research Center, Helsinki, Finland.
- Corresponding author: Jorma Ilonen, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0300/-/DC1.
- Received February 21, 2013.
- Accepted June 20, 2013.
- © 2013 by the American Diabetes Association.
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