title: Development of autoimmunity to transglutaminase C in children of patients with type 1 diabetes: relationship to islet autoantibodies and infant feeding.
abstract: OBJECTIVE
  Coeliac disease and transglutaminase antibodies are common in patients with type 1 diabetes and their relatives. We investigated the development of transglutaminase antibodies and analysed potential risk factors for coeliac disease autoimmunity in first-degree relatives of patients with type 1 diabetes.
  
  
  METHODS
  The study was conducted by prospective observational follow-up from birth of 1,511 children at increased risk of type 1 diabetes or coeliac disease born in Germany between 1989 and 2000. Mean follow-up was to age 7.6 years. Children were tested for transglutaminase and islet autoantibodies. Children were classified as transglutaminase antibody-positive if antibodies were detected by both ELISA and radiobinding assays.
  
  
  RESULTS
  The risk of developing transglutaminase antibodies was 4.9% by age 8 years (n=63; 95% CI, 3.7-6.1%). Transglutaminase antibodies developed at an older age than islet autoantibodies (median age, 4.9 vs 2.3 years; p<0.005), and only three children developed both transglutaminase antibodies and islet autoantibodies. Multivariate analysis indicated an increased risk of transglutaminase antibodies in children with the HLA-DRB1*03 allele (hazard ratio for heterozygous DR3, 5.5; 95% CI, 2.9-10.2; hazard ratio for homozygous DR3, 16.2; 95% CI, 6.7-39; p<0.0001) and in children with impaired uterine growth (birth weight < or = 1st percentile, hazard ratio, 3.1; 95% CI, 1.1-7.8, p=0.03). Neither breast-feeding or its duration nor the age of first exposure to gluten was associated with the risk of developing transglutaminase antibodies.
  
  
  CONCLUSIONS
  Coeliac disease autoimmunity is initiated later than islet autoimmunity in children who are at risk. An influence of infant nutrition on the development of coeliac disease autoimmunity could not be confirmed in this prospective study.
authors.affiliation: Diabetes Research Institute, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hummel
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: J
authors.initials: J
authors.lastname: Banholzer
authors.forename: D
authors.initials: D
authors.lastname: Hanak
authors.forename: U
authors.initials: U
authors.lastname: Mollenhauer
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
authors.forename: A G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D002446:Celiac Disease / Q000201:enzymology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007225:Infant Food; D007515:Islets of Langerhans / Q000276:immunology*; D015999:Multivariate Analysis; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011795:Surveys and Questionnaires; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins