ArticleThe American journal of gastroenterology2015
HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study.
Article in The American journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Genome-Wide Association Study Reveals a Causal Relationship Between Allergic Rhinitis and Hazelnut Allergy.Allergy · 2025Pooled it
- Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk.Nature metabolism · 2026Article
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- Impact of placental and peripheral blood DNA methylation on celiac disease susceptibility.Journal of pediatric gastroenterology and nutrition · 2025Article
- Looking back at the TEDDY study: lessons and future directions.Nature reviews. Endocrinology · 2025Review
- Article
- Coeliac disease: what can we learn from prospective studies about disease risk?The Lancet. Child & adolescent health · 2024Review
- HLA-DQ2/8 and COVID-19 in Celiac Disease: Boon or Bane.Microorganisms · 2023Article
- Human Leukocyte Antigen (HLA) Modulates the Dependence on Age of the Variability of Synchronous Neural Interactions.Neuroscience insights · 2023Article
- Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans.Brain, behavior, & immunity - health · 2022Article
- HLA class II variants defined by next generation sequencing are associated with sarcoidosis in Korean patients.Scientific reports · 2022Article
- Epidemiology and genetics of granulomatosis with polyangiitis.Rheumatology international · 2021Review
- Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity.Diabetes/metabolism research and reviews · 2020Review
- Article
- The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update.Current diabetes reports · 2018Review
- Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity.Pediatrics · 2017Article
- Incidence of Type 1 Diabetes Is Not Increasing in a Population-Based Cohort in Olmsted County, Minnesota, USA.Mayo Clinic proceedings · 2016Article
- Environmental factors in the etiology of type 1 diabetes, celiac disease, and narcolepsy.Pediatric diabetes · 2016Review
- Article
- Gluten consumption during late pregnancy and risk of celiac disease in the offspring: the TEDDY birth cohort.The American journal of clinical nutrition · 2015Observational
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Authors and funding
16 authors at 10 institutions in 5 countries.
Funding
Abstract
objectivesTissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs.
methodsThe Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex.
resultsAfter adjustment for DR3-DQ2 and restriction to allele frequency (AF) ≥5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013).
conclusionsHLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.
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