The first signs of B-cell autoimmunity appear in infancy in genetically susceptible children from the general population: The Finnish Type 1 DiabetesPrediction and Prevention Study

Little is known about the timing of the etiological events and the preclini cal process of type 1 diabetes during the first years of life in the genera l population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of beta -cell au toimmunity and the development of type I diabetes were monitored from birth . Of 25,983 newborn infants, 2,448 genetically susceptible children were mo nitored for islet cell antibodies (ICA) at 3- to 6-month intervals. If an i nfant seroconverted to ICA positivity, all his/her samples were also analyz ed for insulin autoantibodies (IAA), antibodies to the 65-kDa isoform of gl utamic acid decarboxylase, and antibodies to the protein tyrosine phosphata se-related IA-2 molecule. Fifteen children of those who carried the high-ri sk genotype (2.7%) and 23 of those who carried the moderate-risk genotype ( 1.2%; P = 0.019) tested positive for ICA at least once. Among those who sho wed positivity for at least 2 antibodies during the observation period (25 of 38), IAA appeared as the first or among the first antibodies in 22 child ren (88%) and emerged earlier than the other antibodies (P < 0.019 or less) . The first autoantibodies appeared in the majority of the children in the fall and winter (30 of 38 vs. 8 of 38 in the spring and summer, P < 0.001). These observations suggest that young children in the general population w ith a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diab etes show signs of beta -cell autoimmunity proportionally more often than t hose with a moderate genetic risk. IAA emerge as the first detectable antib ody more commonly than any other antibody specificity, implying that insuli n may be the primary antigen in most cases of human type 1 diabetes associa ted with the DR4-DQB1*0302 haplotype. The seasonal variation in the emergen ce of the first signs of beta -cell autoimmunity suggests that infectious a gents may play a role in the induction of such autoimmunity.