Karita Sadeharju

Karita Sadeharju: Maternal and childhood enterovirus infections and the risk of beta-cell autoimmunity Type 1 diabetes is a chronic disease, which is caused by the destruction of insulin producing pancreatic beta-cells. Beta-cells are destroyed by immune mediated mechanisms and the disease is classified as an autoimmune disease. The pathogenesis of the disease is multifactorial. Genetic susceptibility modulates the risk of type 1 diabetes, and HLA locus includes the major genetic susceptibility determinants which are connected to increased or decreased risk of type 1 diabetes. Previous studies have suggested that enterovirus infections are potential risk factors for type 1 diabetes. In the present study the effect of HLA-DR alleles, associated with either the decreased or increased risk of type 1 diabetes, on enterovirus immunity was studied. The role of enterovirus infections in the pathogenesis of type 1 diabetes was evaluated comparing children’s and their mothers’ enterovirus antibody levels and frequency of enterovirus infections from the pregnancy to the age of 24 to 36 months in prospective birth-cohort series. In addition, the effect of maternal antibodies (acquired transplacentally or in breast milk) on child’s enterovirus infections was analysed. Study subjects were from three different studies; DiMe, DIPP and TRIGR. Main results: Enterovirus infections were common showing a peak incidence at the age of 18 months (follow-up until the age of 3 years). Enterovirus viremia was the most frequent at the age of 9 months. Infections were more frequent among boys than girls. Children with diabetes associated autoantibodies had more enterovirus infections and higher levels of enterovirus antibodies than matched control children. They also had their enterovirus infections earlier than control children. Children whose mothers had particularly high enterovirus antibody levels in breast milk had fewer enterovirus infections than other children during the first year of life. Children with either the HLADR3 or -DR4 risk allele for type 1 diabetes had higher enterovirus antibody levels than children carrying the protective HLA-DR2 allele. The results suggest that HLA-DR alleles, which mediate increased susceptibility to type 1 diabetes, are associated with strong humoral immune responses against enteroviruses. The