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

Abstract

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).