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

Kemppainen, Kaisa M; Lynch, Kristian F. LU ; Liu, Edwin; Lönnrot, Maria; Simell, Ville; Briese, Thomas; Koletzko, Sibylle; Hagopian, William; Rewers, Marian and She, Jin-Xiong, et al. (2017) In Clinical Gastroenterology and Hepatology 15(5). p.5-702
Abstract

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... (More)

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.

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subject
keywords
Autoimmunity, Food, Gastroenteritis, Rotavirus
in
Clinical Gastroenterology and Hepatology
volume
15
issue
5
pages
5 - 702
publisher
Elsevier
external identifiers
  • scopus:85013191550
  • wos:000401101600016
ISSN
1542-3565
DOI
10.1016/j.cgh.2016.10.033
language
English
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yes
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12b2cf65-db96-4391-840a-ffc5eb7a2eda
date added to LUP
2017-03-02 10:41:41
date last changed
2018-01-14 04:30:42
@article{12b2cf65-db96-4391-840a-ffc5eb7a2eda,
  abstract     = {<p>Background &amp; 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.</p>},
  author       = {Kemppainen, Kaisa M and Lynch, Kristian F. and Liu, Edwin and Lönnrot, Maria and Simell, Ville and Briese, Thomas and Koletzko, Sibylle and Hagopian, William and Rewers, Marian and She, Jin-Xiong and Simell, Olli and Toppari, Jorma and Ziegler, Anette-G and Akolkar, Beena and Krischer, Jeffrey P and Lernmark, Åke and Hyöty, Heikki and Triplett, Eric W and Agardh, Daniel},
  issn         = {1542-3565},
  keyword      = {Autoimmunity,Food,Gastroenteritis,Rotavirus},
  language     = {eng},
  number       = {5},
  pages        = {5--702},
  publisher    = {Elsevier},
  series       = {Clinical Gastroenterology and Hepatology},
  title        = {Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life},
  url          = {http://dx.doi.org/10.1016/j.cgh.2016.10.033},
  volume       = {15},
  year         = {2017},
}