Evidence map›Paper›PMID 27840181›Full record

ArticleClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association2017

Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life.

Kaisa M Kemppainen, Kristian F Lynch, Edwin Liu, Maria Lönnrot, Ville Simell, Thomas Briese, Sibylle Koletzko, William Hagopian, Marian Rewers, Jin-Xiong She and 10 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05094232 (Epidemiologic Evolution of Coeliac Disease in Spain and Risk Factors Influencing Disease Prevalence), which is not on this map. Cited by 97 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 3 pooled it
12.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

NCT05094232 completednot on this mapstarted 2020, after this paper: background citation

Epidemiologic Evolution of Coeliac Disease in Spain and Risk Factors Influencing Disease Prevalence

TypeobservationalSponsorHospital Mutua de TerrassaRan2020 to 2025Enrolled4,826ConditionsCeliac Disease
3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 183 citations in OpenAlex.

  1. Viruses and celiac disease: what do we know ?Clinical and experimental medicine · 2023
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  16. Is the microbiome important in celiac disease?Journal of the Canadian Association of Gastroenterology · 2025
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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 12 institutions in 4 countries.

Kaisa M KemppainenDepartment of Microbiology and Cell Science, University of Florida, Gainesville, Florida.
Kristian F LynchHealth Informatics Institute, University of South Florida, Tampa, Florida.
Edwin LiuDigestive Health Institute, Children's Hospital Colorado, University of Colorado, Denver; Barbara Davis Center, University of Colorado Denver, Aurora, Colorado.
Maria LönnrotDepartment of Virology, School of Medicine, University of Tampere, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland.
Ville SimellMediCity Laboratory, University of Turku, Turku, Finland.
Thomas BrieseCenter for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Sibylle KoletzkoDr von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany.
William HagopianPacific Northwest Diabetes Research Institute, Seattle, Washington.
Marian RewersDigestive Health Institute, Children's Hospital Colorado, University of Colorado, Denver; Barbara Davis Center, University of Colorado Denver, Aurora, Colorado.
Jin-Xiong SheCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Olli SimellResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Jorma ToppariDepartment of Pediatrics, University of Turku, Turku, Finland; Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
Anette-G ZieglerInstitute of Diabetes Research, Helmholtz Zentrum München, Klinikum Rechts der Isar, Technische Universität München, Forschergruppe Diabetes eV, Neuherberg, Germany.
Beena AkolkarNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Jeffrey P KrischerHealth Informatics Institute, University of South Florida, Tampa, Florida.
Åke LernmarkDepartment of Clinical Sciences, Lund University, Malmo, Sweden.
Heikki HyötyDepartment of Virology, School of Medicine, University of Tampere, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
Eric W TriplettDepartment of Microbiology and Cell Science, University of Florida, Gainesville, Florida.
Daniel AgardhDepartment of Clinical Sciences, Lund University, Malmo, Sweden. Electronic address: daniel.agardh@med.lu.se.
TEDDY Study Group
University of Turku · FIChildren's Hospital Colorado · USLund University · SETampere University · FIUniversity of Florida · USUniversity of South Florida · USAugusta University · USColumbia University · USHelmholtz Zentrum München · DELudwig-Maximilians-Universität München · DENational Institute of Diabetes and Digestive and Kidney Diseases · USPacific Northwest Diabetes Research Institute · US

Funding

Data Coordinating Center (DCC)for the Consortium for Identification of EnvironmenUC4DK095300 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2011 to 2011
$56.0M
Data Coordinating CenterU01DK063790 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2002 to 2006
$50.1M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Using social networks to map and evaluate team science across CTSA hubsUL1TR001427 · NCATS · UNIVERSITY OF FLORIDA · PI MITCHELL, DUANE A. · 2015 to 2024
$37.2M
NIDDK Follow-up on Subjects and Immunological Assessments in The Environmental Determinants of Diabetes In The Young Study (TEDDY) (UC4)UC4DK117483 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2017 to 2020
$30.4M
Establish a Data Coordinating Center (DCC) for the Consortium for Identification UC4DK100238 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2014 to 2014
$28.9M
The Study of Epigenetics and Infections in The Environmental Determinants of Diabetes in the Young (TEDDY)UC4DK112243 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2016 to 2016
$27.0M
Data Coordinating Center (DCC) for the Consortium for Identification of Environmental Determinants of Diabetes in the Young (TEDDY) StudyUC4DK106955 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2015 to 2015
$20.0M
The Environmental Determinants of Diabetes in Young (TEDDY0U01DK063863 · NIDDK · HOSPITAL DISTRICT OF SOUTHWEST FINLAND · PI TOPPARI, JORMA · 2003 to 2022
$13.5M
The Environmental Triggers of Diabetes (TEDDY) in SwedenU01DK063861 · NIDDK · UNIVERSITY OF WASHINGTON · PI LERNMARK, AKE · 2003 to 2022
$13.4M
THE TEDDY STUDY - COLORADO CLINICAL CENTERU01DK063821 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI REWERS, MARIAN J · 2003 to 2022
$12.3M
The TEDDY Study: Georgia/Florida Clinical CenterU01DK063865 · NIDDK · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MCINDOE, RICHARD A. · 2003 to 2022
$12.3M
NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR001082NCATS NIH HHS UL1 TR001427NIDDK NIH HHS HHSN267200700014CNIDDK NIH HHS U01 DK063790NIDDK NIH HHS U01 DK063821NIDDK NIH HHS U01 DK063829NIDDK NIH HHS U01 DK063836NIDDK NIH HHS U01 DK063861NIDDK NIH HHS U01 DK063863NIDDK NIH HHS U01 DK063865NIDDK NIH HHS UC4 DK063821NIDDK NIH HHS UC4 DK063829NIDDK NIH HHS UC4 DK063836NIDDK NIH HHS UC4 DK063861NIDDK NIH HHS UC4 DK063863NIDDK NIH HHS UC4 DK063865NIDDK NIH HHS UC4 DK095300NIDDK NIH HHS UC4 DK100238NIDDK NIH HHS UC4 DK106955NIDDK NIH HHS UC4 DK112243NIDDK NIH HHS UC4 DK117483
6 · The paper itself

Abstract

BACKGROUND &

aimsLittle is known about the pathogenic mechanisms of gluten immunogenicity in patients with celiac disease. We studied temporal associations between infections and the development of celiac disease autoimmunity, and examined effects of HLA alleles, rotavirus vaccination status, and infant feeding.

methodsWe monitored 6327 children in the United States and Europe carrying HLA risk genotypes for celiac disease from 1 to 4 years of age for presence of tissue transglutaminase autoantibodies (the definition of celiac disease autoimmunity), until March 31, 2015. Parental reports of gastrointestinal and respiratory infections were collected every third month from birth. We analyzed time-varying relationships among reported infections, rotavirus vaccination status, time to first introduction of gluten, breastfeeding, and risk of celiac disease autoimmunity using proportional hazard models.

resultsWe identified 13,881 gastrointestinal infectious episodes (GIE) and 79,816 respiratory infectious episodes. During the follow-up period, 732 of 6327 (11.6%) children developed celiac disease autoimmunity. A GIE increased the risk of celiac disease autoimmunity within the following 3 months by 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.11-1.59). This risk increased 2-fold among children born in winter and introduced to gluten before age 6 months (HR, 2.08; 95% CI, 1.46-2.98), and increased 10-fold among children without HLA-DQ2 alleles and breastfed for fewer than 4 months (HR, 9.76; 95% CI, 3.87-24.8). Risk of celiac disease autoimmunity was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR, 0.57; 95% CI, 0.36-0.88).

conclusionsGastrointestinal infections increase the risk of celiac disease autoimmunity in children with genetic susceptibility to this autoimmune disorder. The risk is modified by HLA genotype, infant gluten consumption, breastfeeding, and rotavirus vaccination, indicating complex interactions among infections, genetic factors, and diet in the etiology of celiac disease in early childhood.

Indexed as

AdultCeliac DiseaseChild, PreschoolDietDisease SusceptibilityEuropeFemaleGastroenteritisGenotypeHLA AntigensHumansInfantInfant, NewbornMaleProspective StudiesRespiratory Tract InfectionsHLA AntigensRotavirus VaccinesAutoimmunityFoodGastroenteritisRotavirus

Identifiers

PMID27840181
PMCPMC5576726
OpenAlexW2550497752

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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 OpenQuestion graph.