Microbial associations and viruses on the risk of celiac disease (MAVRiC): a longitudinal post-hoc case-cohort study

Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), was confirmed in 704 of the 6132 genetically at-risk TEDDY children. Celiac disease onset (CD-onset) was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis on CD-onset and CDA children with no diagnosis (CDA-only) revealed female-sex, HLA and non-HLA genes and higher gluten-consumption correlate with an increased risk of both outcomes. However, reports of virus-related respiratory infections from August to October correlate consistently with an increased risk of CD-onset and not CDA-only. A sub-cohort of 561 children (9% sampling fraction) has been randomly selected to represent the TEDDY cohort. All incident CD-onset cases (N = 306) were included. The case-cohort will be utilized to analyze virus antibodies and bacteriome from longitudinal plasma and stool samples (the Microbial Associations and Viruses on the Risk of Celiac disease study, MAVRiC).