ArticleJournal of autoimmunity2018
Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies.
Article in Journal of autoimmunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis.Epidemiology and infection · 2018Pooled it
- Dietary vitamin C intake and the risk of islet autoimmunity and type 1 diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY) Study.European journal of nutrition · 2026Observational
- Thyroid autoimmunity and the subsequent development of islet and celiac autoimmunity in the TEDDY study.American journal of epidemiology · 2026Article
- The diabetes exposome: interplay of environmental and genetic determinants in diabetes.Human genomics · 2026Review
- The Contribution of BMI to a Young Child's Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2.Diabetes care · 2025Article
- Unfolding the Mystery of Autoimmunity: The Environmental Determinants of Diabetes in the Young (TEDDY) Study.Diabetes care · 2025Review
- Respiratory infections in pregnancy and early life-association with the development of islet autoimmunity and type 1 diabetes in children: systematic review and meta-analysis of observational studies.EClinicalMedicine · 2025Article
- Looking back at the TEDDY study: lessons and future directions.Nature reviews. Endocrinology · 2025Review
- Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.Scientific reports · 2024Article
- Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study.Diabetes care · 2023Article
- Possible heterogeneity of initial pancreatic islet beta-cell autoimmunity heralding type 1 diabetes.Journal of internal medicine · 2023Review
- CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.Clinical and experimental immunology · 2023Article
- Respiratory infections and type 1 diabetes: Potential roles in pathogenesis.Reviews in medical virology · 2023Review
- Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories.Nature communications · 2022Article
- Viruses and Type 1 Diabetes: From Enteroviruses to the Virome.Microorganisms · 2021Review
- Etiology of Autoimmune Islet Disease: Timing Is Everything.Diabetes · 2021Review
- Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes.Diabetologia · 2021Observational
- First-appearing islet autoantibodies for type 1 diabetes in young children: maternal life events during pregnancy and the child's genetic risk.Diabetologia · 2021Article
- The clinical consequences of heterogeneity within and between different diabetes types.Diabetologia · 2020Review
Corrections and comments
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Authors and funding
18 authors at 11 institutions in 4 countries.
Funding
Abstract
β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patterned by T1D-associated genes, suggesting an early environmental influence. Here, we tested if gestational infections and interactions with child's human leukocyte antigen (HLA) and non-HLA genes affected the appearance of the first β-cell autoantibody. Singletons of mothers without diabetes (n = 7472) with T1D-associated HLA-DR-DQ genotypes were prospectively followed quarterly through the first 4 years of life, then semiannually until age 6 years, using standardized autoantibody analyses. Maternal infections during pregnancy were assessed via questionnaire 3-4.5 months post-delivery. Polymorphisms in twelve non-HLA genes associated with the first appearing β-cell autoantibodies were included in a Cox regression analysis. IAA predominated as the first appearing β-cell autoantibody in younger children (n = 226, median age at seroconversion 1.8 years) and GADA (n = 212; 3.2 years) in children aged ≥2 years. Gestational infections were not associated with the first appearing β-cell autoantibodies overall. However, gestational respiratory infections (G-RI) showed a consistent protective influence on IAA (HR 0.64, 95% CI 0.45-0.91) among CTLA4-(AG, GG) children (G-RI*CTLA4 interaction, p = 0.002). The predominant associations of HLA-DR-DQ 4-8/8-4 with IAA and HLA-DR-DQ 3-2/3-2 with GADA were not observed if a G-RI was reported (G-RI*HLA-DR-DQ interaction, p = 0.03). The role of G-RI may depend on offspring HLA and CTLA-4 alleles and supports a bidirectional trigger for IAA or GADA as a first appearing β-cell autoantibody in early life.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.