Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life.
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.
['Kemppainen|Kaisa M|KM|', 'Lynch|Kristian F|KF|', 'Liu|Edwin|E|', 'Lönnrot|Maria|M|', 'Simell|Ville|V|', 'Briese|Thomas|T|', 'Koletzko|Sibylle|S|', 'Hagopian|William|W|', 'Rewers|Marian|M|', 'She|Jin-Xiong|JX|', 'Simell|Olli|O|', 'Toppari|Jorma|J|', 'Ziegler|Anette-G|AG|', 'Akolkar|Beena|B|', 'Krischer|Jeffrey P|JP|', 'Lernmark|Åke|Å|', 'Hyöty|Heikki|H|', 'Triplett|Eric W|EW|', 'Agardh|Daniel|D|', '|||']
D000328:Adult D002446:Celiac Disease D002675:Child, Preschool D004032:Diet D004198:Disease Susceptibility D005060:Europe D005260:Female D005759:Gastroenteritis D005838:Genotype D006680:HLA Antigens D006801:Humans D007223:Infant D007231:Infant, Newborn D008297:Male D011446:Prospective Studies D012141:Respiratory Tract Infections D018570:Risk Assessment D012401:Rotavirus D022243:Rotavirus Vaccines D014481:United States
Autoimmunity Rotavirus Food Gastroenteritis