Patterns of ß-cell Autoantibody Appearance and Genetic Associations During the First Years of Life

  1. Mikael Knip6,7,8
  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 and Turku University Hospital,
  4. 4Immune Response Unit, National Institute for Health and Welfare, Helsinki, Finland,
  5. 5Institute of Clinical Medicine, Department of Pediatrics, University of Oulu, Oulu and Oulu University Hospital, Finland,
  6. 6Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland,
  7. 7Department of Pediatrics, Tampere University Hospital, Tampere, Finland,
  8. 8Folkhälsan Research Center, Helsinki, Finland
  1. Corresponding author: Jorma Ilonen E-mail: 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 disease risk. In 315 cases a single biochemical autoantibody could be identified in the first positive sample, to insulin (IAA) in 180, to GAD (GADA) in 107 and to islet antigen-2 (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 of appearance during the second year of life, whereas GADA as the first autoantibody peaked later between age 3 to 5. The risk associated insulin gene rs689 AA genotypes were more frequent in children with IAA as the first autoantibody compared to 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 19, 2013.

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