TY - JOUR
T1 - Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures
AU - Colorado Clinical Center
AU - Previously
AU - TEDDY study group
AU - Other contributors
AU - Repository
AU - HLA Reference Laboratory
AU - Genetics Laboratory
AU - Autoantibody Reference Laboratories
AU - Project Scientist
AU - Data Coordinating Center
AU - Pennsylvania Satellite Center
AU - Washington Clinical Center
AU - Sweden Clinical Center
AU - Germany Clinical Center
AU - Georgia/Florida Clinical Center
AU - Finland Clinical Center
AU - Eurén, Anna
AU - Lynch, Kristian
AU - Lindfors, Katri
AU - Parikh, Hemang
AU - Koletzko, Sibylle
AU - Liu, Edwin
AU - Akolkar, Beena
AU - Hagopian, William
AU - Krischer, Jeffrey
AU - Rewers, Marian
AU - Toppari, Jorma
AU - Ziegler, Anette
AU - Agardh, Daniel
AU - Kurppa, Kalle
AU - Triplett, Eric
AU - Thorsen, Steffen Ullitz
AU - Pastinen, Tomi
AU - McKinney, Eoin
AU - Johnson, Suzanne Bennett
AU - Brusko, Todd
AU - Briese, Thomas
AU - Mulholland, Niveen
AU - Ke, Sandra
AU - Fear, Anna Lisa
AU - Mack, Steven J.
AU - Erlich, Henry
AU - Tucker, Preston
AU - Radtke, Jared
AU - Campolieto, Paul
AU - Bonnie, Jessica
AU - Gallo, Dan
AU - Davis, Jordan
AU - Davis, Jonathan
AU - Pickin, Rebecca Roche
AU - Farber, Emily
AU - Onengut-Gumuscu, Suna
AU - Chen, Wei Min
AU - Rich, Stephen S.
AU - Randell, Matthew
AU - Khoud, Yassin Ben
AU - Kelland, Ilana
AU - Chandler, Kyla
AU - Gillespie, Kathleen
AU - Miao, Dongmei
AU - Yu, Liping
AU - Smith, Laura
AU - Quigley, Ryan
AU - Meulemans, Steven
AU - Sharma, Ashok
AU - McIndoe, Richard
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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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U2 - 10.1038/s41598-024-75496-w
DO - 10.1038/s41598-024-75496-w
M3 - Article
C2 - 39462122
AN - SCOPUS:85207848859
SN - 2045-2322
VL - 14
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 25463
ER -