A1 Refereed original research article in a scientific journal
Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures
Authors: Eurén, Anna; Lynch, Kristian; Lindfors, Katri; Parikh, Hemang; Koletzko, Sibylle; Liu, Edwin; Akolkar, Beena; Hagopian, William; Krischer, Jeffrey; Rewers, Marian; Toppari, Jorma; Ziegler, Anette; Agardh, Daniel; Kurppa, Kalle; & TEDDY Study Group
Publisher: Nature Portfolio
Publication year: 2024
Journal: Scientific Reports
Journal name in source: Scientific Reports
Article number: 25463
Volume: 14
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-024-75496-w
Web address : https://doi.org/10.1038/s41598-024-75496-w
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/459054688
Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study. Altogether 6523 genetically predisposed children were enrolled to long-term follow-up with prospective sampling and data collection at six research centers in the USA, Germany, Sweden and Finland. Celiac disease autoimmunity was defined as positive tissue transglutaminase antibodies in two consecutive serum samples. There was a significant season of birth effect on the risk of celiac autoimmunity. The effect was dependent on polymorphisms in CD247 gene encoding for CD3ζ chain of TCR-CD3 complex. In particular, children with major alleles for SNP rs864537A > G, in CD247 (AA genotype) had an excess risk of celiac autoimmunity when born March–August as compared to other months. The interaction of CD247 with season of birth on autoimmunity risk was accompanied by interactions with febrile infections between the ages of 3–6 months. Considering the important role of TCR-CD3 complex in the adaptive immune response and our findings here, CD247 variants and their possible effect of subgroups in autoimmunity development could be of interest in the design of future gene-environment studies of celiac disease. ClinicalTrials.gov Identifier: NCT00279318.
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Funding information in the publication:
The study was supported specifically by the Foundation for Pediatric Research, the Competitive State Research Financing of the Expert Area of Tampere University Hospital, the Päivikki and Sakari Sohlberg Foundation. TEDDY is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and Breakthrough T1D (formerly JDRF). A part of this work is supported by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
