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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
  • Olli Simell
  • Jorma Toppari
  • Anette-G Ziegler
  • Beena Akolkar
  • Jeffrey P Krischer
  • Åke Lernmark
  • Heikki Hyöty
  • Eric W Triplett
  • Daniel Agardh
Publishing year: 2017
Language: English
Pages: 5-702
Publication/Series: Clinical Gastroenterology and Hepatology
Volume: 15
Issue: 5
Document type: Journal article
Publisher: Elsevier

Abstract english

Background & Aims: Little 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. Methods: We 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. Results: We 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). Conclusions: Gastrointestinal 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.


  • Gastroenterology and Hepatology
  • Autoimmunity
  • Food
  • Gastroenteritis
  • Rotavirus


  • Diabetes and Celiac Unit
  • ISSN: 1542-3565
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00