Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures

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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Publication Details

Journal
Scientific Reports
Published
2024-10-26
DOI
https://doi.org/10.1038/s41598-024-75496-w
Citations
5
Primary Topic
Celiac Disease Research and Management
Type
article
Field-Weighted Citation Impact
2.32

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article

Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures

Sibylle Koletzko, Katri Lindfors, Beena Akolkar, Edwin Liu et al.
5 citations
Scientific Reports
Celiac Disease Research and Management
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article

Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures

Sibylle Koletzko, Katri Lindfors, Beena Akolkar, Edwin Liu, Kristian Lynch, William Hagopian, Hemang M. Parikh, Daniel Agardh, Kalle Kurppa, Marian J. Rewers, Jeffrey Krischer, Anna Eurén, Jorma Toppari, Anette G. Ziegler
article en
5 citations

Abstract

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.

Scientific ReportsVol. 14(1)
Florida State University (US), University of Copenhagen (DK), Pacific Northwest Diabetes Research Institute (US), Children’s Institute (US), Children's Mercy Hospital (US), University of Bonn (DE), University of Turku (FI), Tampere University (FI), Seinäjoki University of Applied Sciences (FI), Lund University (SE), University of Cambridge (GB), Augusta University (US), University of South Florida (US), Oulu University Hospital (FI), Turku University Hospital (FI), Copenhagen University Hospital (DK), TUM Klinikum (DE), Helmholtz Zentrum München (DE), University of Florida (US), University of Bristol (GB), Finnish Institute for Health and Welfare (FI), National Institute of Diabetes and Digestive and Kidney Diseases (US), Children's Hospital Colorado (US), Tampere University Hospital (FI), Varsinais-Suomen Sairaanhoitopiiri (FI), Children's Hospital of Pittsburgh (US), Tampere University (FI), Fisher Bioservices (United States) (US), Seinäjoen Keskussairaala (FI), German Center for Diabetes Research (DE), Institute of Diabetes Research, Indiana University School of Medicine, University of Warmia and Mazury in Olsztyn (PL), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), Indiana University – Purdue University Indianapolis (US), Technical University of Munich (DE), Columbia University (US), Technische Universität Dresden (DE), Ludwig-Maximilians-Universität München (DE), University of Colorado Denver (US), University of Oulu (FI)
Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
Openalex Percentile: Top 11%
Celiac Disease Research and Management
2.32
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