title: Development of celiac disease-associated antibodies in offspring of parents with type I diabetes.
abstract: OBJECTIVE
  The aim of this study was to determine the frequency and temporal development of antibodies related to celiac disease in offspring of parents with Type I (insulin-dependent) diabetes mellitus.
  
  
  METHODS
  Sera from 913 offspring of parents with Type I diabetes prospectively followed from birth to the age of 8 years were tested for IgG-transglutaminase antibodies (IgG-tTGCAs), endomysial IgA antibodies (EMA) and gliadin antibodies.
  
  
  RESULTS
  We found tTGCAs in 32 (3.5%) of the 913 relatives. Prevalence was related to age and reached 6.5% at age 8 years. Endomysial IgA antibodies were detected in 44% of the relatives with tTGCAs and 0.6% of tTGCA negative relatives and were also most prevalent (5 %) in those aged 8 years. Both tTGCAs and EMAs were more frequent in relatives with the HLA DRB1*03 DQA1*0501 DQB1*02 haplotype (7.1% and 7.2%, respectively; p < 0.005). Antigliadin antibodies were common in both tTGCA positive (42%) and negative (23%) relatives, did not show a relation with age and were less prevalent in relatives with HLA DR3 (p < 0.05). There was no association between the presence of antibodies associated with celiac disease and islet autoantibodies in these relatives. Of the relatives 15 (1.6%) had tTGCAs plus EMAs. In two of these, anti-gliadin antibodies were detected before the detection of tTGCAs and EMAs at the age of 9 months whereas none of the remainder had any antibodies associated with celiac disease before age 2 years. In three there were no detectable antigliadin antibodies in any of the samples tested. Celiac disease without clinical symptoms was diagnosed in 9 of 12 by intestinal biopsy. CONCLUSION/INTERPRETATION. A statistically significant proportion of relatives of patients with Type I diabetes have celiac disease-associated autoimmunity and the silent form of celiac disease early in life. These relatives should, therefore, be considered for celiac antibody screening.
authors.affiliation: Diabetes Research Institute and 3rd Medical Department, Academic Teaching Hospital München-Schwabing, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: J
authors.initials: J
authors.lastname: Dittler
authors.forename: A
authors.initials: A
authors.lastname: Schimmel
authors.forename: A G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002446:Celiac Disease / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005903:Gliadin / Q000276:immunology*; D006681:HLA-D Antigens / Q000097:blood; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007231:Infant, Newborn; D008137:Longitudinal Studies; D009679:Nuclear Family; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006681:HLA-D Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005903:Gliadin; D011503:Transglutaminases