Patterns of β-Cell Autoantibody Appearance and Genetic Associations During the First Years of Life

  1. Mikael Knip8,9,10,11
  1. 1Immunogenetics Laboratory, University of Turku, Turku, Finland
  2. 2Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland
  3. 3Department of Pediatrics, University of Turku, Turku, Finland
  4. 4Turku University Hospital, Turku, Finland
  5. 5Immune Response Unit, National Institute for Health and Welfare, Helsinki, Finland
  6. 6Department of Pediatrics, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
  7. 7Oulu University Hospital, Oulu, Finland
  8. 8Children’s Hospital, University of Helsinki, Helsinki, Finland
  9. 9Helsinki University Hospital, Helsinki, Finland
  10. 10Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  11. 11Folkhälsan Research Center, Helsinki, Finland.
  1. Corresponding author: Jorma Ilonen, jorma.ilonen{at}


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.


  • Received February 21, 2013.
  • Accepted June 20, 2013.


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  1. Diabetes vol. 62 no. 10 3636-3640
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