Year: 2026
Type: dissertation
Study design: Observational Study
Abstract: Immune-mediated diseases such as celiac disease (CD) and type 1 diabetes (T1D) arise from complex interactions between genetic susceptibility and environmental exposures.Increasing evidence suggests that the process leading to immune dysregulation may begin early in life, potentially already during fetal development, and continue throughout childhood before clinical disease manifests.CD is one of the most common autoimmune diseases in childhood, yet a substantial proportion of affected individuals remain undiagnosed without screening.Longitudinal cohort studies provide important opportunities to better understand the natural history of CD and the environmental and immunological factors contributing to disease development.The overall aim of this thesis was to investigate early-life determinants of CD and related immunemediated diseases across different developmental stages.The first aim was to perform a screening in children both with and without genetic risk for CD up to age 15 years.The second aim was to investigate associations between residential environment and CD development.The third aim was to examine whether maternal inflammatory markers in the first trimester and at delivery are associated with offspring's risk of immune-mediated disease with emphasis on CD.The fourth aim was to evaluate associations between maternal pathogen-specific antibody levels during pregnancy and offspring's risk of CD and T1D.Studies I and II were based on the Celiac Prediction in Skåne (CiPiS) cohort, which included children born in southern Sweden between 2001 and 2004.Overall, 29,039 infants were HLA-DQ genotyped at birth and invited to screening for CD using tissue transglutaminase autoantibodies (tTGA) at ages 3, 9 and 15 years.CD was confirmed by duodenal biopsy in children detected positive for tTGA at any of these time points.In Study II, residential environment exposures were assessed using satellite-derived leaf area index (LAI), normalized difference vegetation index (NDVI) and CORINE land cover data from the CiPiS cohort.In Studies III and IV, maternal first trimester and cord blood samples from the PREDICTA cohort, comprising mother-child pairs followed for CD and T1D within the Environmental Determinants of Diabetes in the Young (TEDDY) study, were analyzed using the OLINK inflammation panel (Study III) and Array-in-Well assays for pathogen-specific antibodies (Study IV).Of the children genotyped at birth, 20.6% were screened at least once in CiPiS, of whom 2.3% were diagnosed with CD, only among children genetically at risk.New CD cases were identified at 15 years.The number of new cases identified at screening declined compared with ages 3 and 9 years.Higher early-life residential greenness (LAI) was associated with CD at ages 3 and 9 years.In analyses of prenatal immune markers, maternal first-trimester levels of IL-5 were associated with offspring CD risk in single protein analysis.No other association was seen for CD.In addition, maternal rotavirus-specific antibody levels were inversely associated with offspring CD risk.The findings of the present thesis support the concept that immune-mediated diseases, particularly CD, may develop through processes operating across the life course, from prenatal immune programming and extending through early-life environmental exposures.The demonstration that CD may develop beyond early childhood supports the potential value of repeated screening strategies, which may be restricted to those at genetic risk.Together, these results contribute to improved understanding of earlylife determinants of CD and provide insight into broader immunological mechanisms relevant to immunemediated disease.
Author: Boström, Michaela
Institution: Lund University
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7159903908