title: Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study.
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 > or = 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.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045-6511, USA.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.forename: Margo C
authors.initials: MC
authors.lastname: Honeyman
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hoffenberg
authors.forename: Joel E
authors.initials: JE
authors.lastname: Haas
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.forename: Lisa
authors.initials: L
authors.lastname: Emery
authors.forename: Iman
authors.initials: I
authors.lastname: Taki
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000502:physiology*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D011503:Transglutaminases / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D006680:HLA Antigens; D011503:Transglutaminases