title: Majority of children with type 1 diabetes produce and deposit anti-tissue transglutaminase antibodies in the small intestine.
abstract: OBJECTIVE
  Anti-tissue transglutaminase (TG2) antibodies are the serological marker of celiac disease. Given the close association between celiac disease and type 1 diabetes, we investigated the production and deposition of anti-TG2 antibodies in the jejunal mucosa of type 1 diabetic children.
  
  
  METHODS
  Intestinal biopsies were performed in 33 type 1 diabetic patients with a normal mucosal architecture: 14 had high levels (potential celiac disease patients) and 19 had normal levels of serum anti-TG2 antibodies. All biopsy specimens were investigated for intestinal deposits of IgA anti-TG2 antibodies by double immunofluorescence. In addition, an antibody analysis using the phage display technique was performed on the intestinal biopsy specimens from seven type 1 diabetic patients, of whom four had elevated and three had normal levels of serum anti-TG2 antibodies.
  
  
  RESULTS
  Immunofluorescence studies showed that 11 of 14 type 1 diabetic children with elevated levels and 11 of 19 with normal serum levels of anti-TG2 antibodies presented with mucosal deposits of such autoantibodies. The phage display analysis technique confirmed the intestinal production of the anti-TG2 antibodies; however, whereas the serum-positive type 1 diabetic patients showed a preferential use of the VH5 antibody gene family, in the serum-negative patients the anti-TG2 antibodies belonged to the VH1 and VH3 families, with a preferential use of the latter.
  
  
  CONCLUSIONS
  Our findings demonstrate that there is intestinal production and deposition of anti-TG2 antibodies in the jejunal mucosa of the majority of type 1 diabetic patients. However, only those with elevated serum levels of anti-TG2 antibodies showed the VH usage that is typical of the anti-TG2 antibodies that are produced in patients with celiac disease.
authors.affiliation: Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Mariantonia
authors.initials: M
authors.lastname: Maglio
authors.forename: Fiorella
authors.initials: F
authors.lastname: Florian
authors.forename: Monica
authors.initials: M
authors.lastname: Vecchiet
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.forename: Francesco
authors.initials: F
authors.lastname: Paparo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Spadaro
authors.forename: Delia
authors.initials: D
authors.lastname: Zanzi
authors.forename: Luciano
authors.initials: L
authors.lastname: Rapacciuolo
authors.forename: Adriana
authors.initials: A
authors.lastname: Franzese
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Roberto
authors.initials: R
authors.lastname: Marzari
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000096:biosynthesis*; D001706:Biopsy; D002446:Celiac Disease / Q000150:complications / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology* / Q000276:immunology*; D019204:GTP-Binding Proteins; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins