Gestational Islet Autoimmunity, Infections, and Type 1 Diabetes

Sammanfattning: The intention of this thesis was to investigate autoimmune markers for type 1 diabetes, together with signs of enterovirus infections during the pre- and perinatal period of life, and their possible association with the development of diabetes during childhood, adolescence, and young adulthood. We found that: 1. Newborns with ABO immunization, linked in epidemiological studies with heightened diabetes risk, had an increased prevalence of islet autoantibodies at birth. This was also observed in newborns with neonatal hyperbilirubinemia without blood-group incompatibility, suggesting that intrauterine factors may be associated with islet autoimmunity. 2. The epitope pattern of GAD65 immunoglobulin binding differed between birth and diagnosis of type 1 diabetes, supporting the view that a change in the epitope pattern sometimes occurs between birth and diagnosis. Moreover, the epitope pattern of the child at birth differed from that of its mother; hence it cannot be completely excluded that the fetus may be capable of some antibody production of its own. 3. Children with fewer islet autoantibodies when diagnosed with type 1 diabetes were more likely to have had autoantibodies in their cord blood sample, leading us to conclude that cord blood islet autoimmunity in offspring of non-diabetic mothers may modulate the immunological expression of diabetes, and explain why some type 1 diabetic children are islet autoantibody negative at the time of clinical diagnosis. 4. Adolescents and young adults who developed type 1 diabetes between ages 15 and 25 had no increased prevalence of any of the four islet autoantibodies at birth, in contrast to an earlier study of children under age 15, showing that pre- and perinatal risk factors are less likely to be involved in the development of type 1 diabetes in young adulthood. 5. Mothers whose offspring developed type 1 diabetes between ages 15 and 25 had slightly higher titers of enterovirus-specific IgM compared to a control group, but the difference was insignificant. However, boys of enterovirus IgM positive mothers had a risk of developing diabetes approximately five times greater than boys of enterovirus IgM negative mothers. Our study could not rule out the possibility that gestational infections might also influence the risk of diabetes in adolescence and young adulthood. Our data support the view that islet autoantibodies at birth are markers of an ongoing process in the ?-cells. Gestational factors appear to be of importance for the risk of developing type 1 diabetes in childhood, and may also influence the risk in adolescence and young adulthood. Pre- and perinatal events also seem to modulate the immunological expression of diabetes during childhood.