Shaping of Adaptive Immunity and Celiac Disease Autoimmunity in a Population based Childhood Cohort : The Generation R Study

The studies described in Part I of this thesis illustrate the complex, and large age-dependent inter-individual variability of immune maturation during childhood from birth until 6 years of age. This variability is largely driven by non-heritable (environmental) factors, of which postnatal herpesvirus acquisition may be considered one of the most profound determinants. Our results stress the ability of the immune system in childhood to suppress a persistent virus, such as herpesviruses, without the negative effects that have been observed in elderly. Second, we observed breastfeeding to transiently increase the child’s cellular immunity, at the expense of humoral immunity, which potentially contributes to the protective effects against infectious diseases in childhood. Furthermore, we provide evidence that the epidemiology of herpesvirus infections in early childhood has not changed substantially during the last half-decade, and we identified several high risk groups that may serve as targets for future prevention strategies of herpesvirus associated diseases.

The studies in Part II describe determinants and consequences of celiac disease autoimmunity in the healthy childhood population. We found celiac disease autoimmunity in childhood to be associated with retardation in weight gain and reduced bone mineral densities, underscoring the need for optimizing earlier diagnosis and treatment. Second, we found screening on tissue-transglutaminase type 2 (TG2A) in the general population of 6-year old children to have a positive predictive value of 61% to detect subclinical celiac disease. As current primary prevention strategies cannot prevent the onset of celiac disease, secondary prevention may be a realistic alternative.