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

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 (greater than or equal to2) 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.