Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction and Prevention Study

Diabetologia. 2003 Jan;46(1):65-70. doi: 10.1007/s00125-002-0976-5. Epub 2002 Dec 18.


Aims/hypothesis: To assess the role of HLA-defined genetic diabetes susceptibility in the appearance of signs of beta-cell autoimmunity in a series of children derived from the general population.

Methods: Tests for five HLA DQB1 alleles and four diabetes-associated autoantibodies were carried out on 1,584 older sibs of infants with an increased HLA-defined genetic risk of Type 1 diabetes. The DQB1 genotypes were classified into those conferring high (* 02/0302), moderate (* 0302/x; where x indicates * 0302 or a non-defined allele), low (* 0301/0302, * 02/0301, * 02/x, * 0302/0602, * 0302/0603; where x indicates * 02 or a non-defined allele) or decreased risk (other genotypes).

Results: Both islet cell antibodies (ICA) and GAD65 antibodies (GADA) were more frequent among the sibs with the high-risk genotype than among those with a low or decreased risk. Insulin autoantibodies and IA-2 antibodies (IA-2A) were more prevalent in the high-risk than low-risk sibs. Sibs with moderate-risk genotypes tested positive for ICA, GADA and IA-2A more often than sibs with genotypes conferring decreased risk. Autoantibody titres were also dependent on the genetic risk with high risk sibs having the highest values. Sibs carrying high-risk or moderate-risk genotypes tested positive for multiple antibodies (> or =2) more often than did the sibs with low or decreased genetic risk.

Conclusions/interpretation: The data show that HLA-defined susceptibility to Type 1 diabetes has an effect on both the quality and quantity of humoral beta-cell autoimmunity in unaffected children derived from the general population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / analysis
  • Autoantibodies / analysis
  • Autoimmunity*
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control
  • Female
  • Finland
  • Genetic Predisposition to Disease*
  • Genotype
  • Glutamate Decarboxylase / immunology
  • HLA Antigens / genetics*
  • Humans
  • Insulin / immunology
  • Islets of Langerhans / immunology*
  • Isoenzymes / immunology
  • Male
  • Prognosis


  • Antibodies
  • Autoantibodies
  • HLA Antigens
  • ICA512 autoantibody
  • Insulin
  • Isoenzymes
  • islet cell antibody
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2