Majority of Children With Type 1 Diabetes Produce and Deposit Anti-Tissue Transglutaminase Antibodies in the Small Intestine

  1. Mariantonia Maglio1,
  2. Fiorella Florian2,
  3. Monica Vecchiet2,
  4. Renata Auricchio1,
  5. Francesco Paparo1,
  6. Raffaella Spadaro1,
  7. Delia Zanzi1,
  8. Luciano Rapacciuolo1,
  9. Adriana Franzese1,
  10. Daniele Sblattero3,
  11. Roberto Marzari2 and
  12. Riccardo Troncone1
  1. 1Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University “Federico II,” Naples, Italy;
  2. 2Department of Health Sciences, University of Trieste, Trieste, Italy;
  3. 3Department of Medical Sciences and Research Centre on Autoimmune Diseases, University of Eastern Piedmont, Novara, Italy.
  1. Corresponding author: Riccardo Troncone, troncone{at}unina.it.

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received July 18, 2008.
    • Accepted April 8, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes vol. 58 no. 7 1578-1584
  1. All Versions of this Article:
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