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Clin Gastroenterol Hepatol. 2017 May;15(5):694-702.e5. doi: 10.1016/j.cgh.2016.10.033. Epub 2016 Nov 10.

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

Author information

1
Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida.
2
Health Informatics Institute, University of South Florida, Tampa, Florida.
3
Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Denver; Barbara Davis Center, University of Colorado Denver, Aurora, Colorado.
4
Department of Virology, School of Medicine, University of Tampere, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland.
5
MediCity Laboratory, University of Turku, Turku, Finland.
6
Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
7
Dr von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany.
8
Pacific Northwest Diabetes Research Institute, Seattle, Washington.
9
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
10
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
11
Department of Pediatrics, University of Turku, Turku, Finland; Departments of Physiology and Pediatrics, University of Turku, Turku, Finland.
12
Institute of Diabetes Research, Helmholtz Zentrum München, Klinikum Rechts der Isar, Technische Universität München, Forschergruppe Diabetes eV, Neuherberg, Germany.
13
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
14
Department of Clinical Sciences, Lund University, Malmo, Sweden.
15
Department 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.
16
Department of Clinical Sciences, Lund University, Malmo, Sweden. Electronic address: daniel.agardh@med.lu.se.

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 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.

KEYWORDS:

Autoimmunity; Food; Gastroenteritis; Rotavirus

PMID:
27840181
PMCID:
PMC5576726
DOI:
10.1016/j.cgh.2016.10.033
[Indexed for MEDLINE]
Free PMC Article

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