Majority of children with type 1 diabetes produce and deposit anti-tissue transglutaminase antibodies in the small intestine

Diabetes. 2009 Jul;58(7):1578-84. doi: 10.2337/db08-0962. Epub 2009 Apr 28.

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.

Research design and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / biosynthesis*
  • Biopsy
  • Celiac Disease / complications
  • Celiac Disease / immunology
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / enzymology*
  • Diabetes Mellitus, Type 1 / immunology*
  • GTP-Binding Proteins
  • HLA Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Immunohistochemistry
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Jejunum / enzymology
  • Jejunum / immunology
  • Jejunum / pathology
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • HLA Antigens
  • Interleukin-2 Receptor alpha Subunit
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins