Rotavirus Infection Frequency and Risk of Celiac Disease Autoimmunity in Early Childhood: A Longitudinal Study

Authors: Stene, Lars C.; Honeyman, Margo C.; Hoffenberg, Edward J.¹; Haas, Joel E.²; Sokol, Ronald J.¹; Emery, Lisa³; Taki, Iman³; Norris, Jill M.³; Erlich, Henry A.⁴; Eisenbarth, George S.⁵; Rewers, Marian

Source: The American Journal of Gastroenterology, Volume 101, Number 10, October 2006 , pp. 2333-2340(8)

Publisher: Blackwell Publishing

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Abstract:

OBJECTIVE: Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity.

METHODS: A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (>2 assay coefficient of variation) in rotavirus antibody between clinic visits.

RESULTS: Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for ≥2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04-3.61, p= 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes.

CONCLUSIONS: This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.

(Am J Gastroenterol 2006;101:2333-2340)

Document Type: Research article

DOI: 10.1111/j.1572-0241.2006.00741.x

Affiliations: 1: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Children's Hospital, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 2: Department of Pathology, The Children's Hospital, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 3: Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 4: Department of Human Genetics, Roche Molecular Systems, Inc, Alameda, California 5: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado

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