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Tissue transglutaminase expression in celiac mucosa: an immunohistochemical study

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Abstract

Tissue transglutaminase (tTG) constitutes the main autoantigen in celiac disease (CD). The aim of the study was to clarify weather celiac disease is associated with changes in tTG expression in duodenal mucosa. Tissue transglutaminase was assessed immunohistochemically (clone CUB 7402) in duodenal biopsy specimens from 22 untreated CD patients, ten normal controls (NC) with unremarkable duodenal mucosa, and nine disease nonceliac controls (DC). In 15 CD patients duodenal biopsy specimens were repeatedly assessed after these patients had been prescribed gluten-free diet. Positive pixel count algorithm of ImageScope was used for quantitative evaluation of immunohistochemistry. Tissue transglutaminase expression in superficial epithelium differed significantly between the three groups (p < 0.001). It was increased in DC in relation to NC (p < 0.001) and in CD—in relation to NC (p < 0.001) and DC (p = 0.003). In CD and DC, cryptal epithelium was stained more intensively than in NC (p < 0.001), but there was no difference between CD and DC (p = 0.507). The same pattern was seen in lamina propria. A significant decrease in tTG expression in all the compartments was seen in repeatedly assessed samples. Untreated CD is associated with tTG overexpression, which is reversible. Tissue transglutaminase up-regulation does not seem to be specific for CD and can appear in other pathological conditions.

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References

  1. Griffin M, Casadio R, Bergamini CM (2002) Transglutaminases: nature's biological glues. Biochem J 368(Pt 2):377–396

    Article  CAS  PubMed  Google Scholar 

  2. Wodzinska JM (2005) Transglutaminases as targets for pharmacological inhibition. Mini Rev Med Chem 5:279–292

    CAS  PubMed  Google Scholar 

  3. Reif S, Lerner A (2004) Tissue transglutaminase—the key player in celiac disease: a review. Autoimmun Rev 3:40–45

    Article  CAS  PubMed  Google Scholar 

  4. van de Wal Y, Kooy Y, van Veelen P et al (1998) Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol 161:1585–1588

    PubMed  Google Scholar 

  5. Arentz-Hansen H, Körner R, Molberg O et al (2000) The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med 191:603–612

    Article  CAS  PubMed  Google Scholar 

  6. Facchiano F, Facchiano A, Facchiano AM (2006) The role of transglutaminase-2 and its substrates in human diseases. Front Biosci 11:1758–1773

    Article  CAS  PubMed  Google Scholar 

  7. Piper JL, Gray GM, Khosla C (2002) High selectivity of human tissue transglutaminase for immunoactive gliadin peptides: implications for celiac sprue. Biochemistry 41:386–393

    Article  CAS  PubMed  Google Scholar 

  8. Dieterich W, Esslinger B, Trapp D et al (2006) Cross-linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease. Gut 55:478–484

    Article  CAS  PubMed  Google Scholar 

  9. Sollid LM, Molberg O, McAdam S et al (1997) Autoantibodies in coeliac disease: tissue transglutaminase—guilt by association? Gut 41:851–852

    Article  CAS  PubMed  Google Scholar 

  10. Barone MV, Caputo I, Ribecco MT et al (2007) Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease. Gastroenterology 132:1245–1253

    Article  CAS  PubMed  Google Scholar 

  11. Maiuri L, Ciacci C, Ricciardelli I et al (2005) Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology 129:1400–1413

    Article  CAS  PubMed  Google Scholar 

  12. Bruce SE, Bjarnason I, Peters TJ (1986) Human jejunal transglutaminase: demonstration of activity, enzyme kinetics, and substrate specificity with special relation to gliadin and coeliac disease. Clin Sci (Lond) 68:573–579

    Google Scholar 

  13. D'Argenio G, Sorrentini I, Ciacci C et al (1989) Human serum transglutaminase and coeliac disease: correlation between serum and mucosal activity in an experimental model of rat small bowel enteropathy. Gut 30:950–954

    Article  PubMed  Google Scholar 

  14. Skovbjerg H, Hansen GH, Niels-Christiansen LL et al (2004) Intestinal tissue transglutaminase in coeliac disease of children and adults: ultrastructural localization and variation in expression. Scand J Gastroenterol 39:1219–1227

    Article  CAS  PubMed  Google Scholar 

  15. Kim SY, Jeitner TM, Steinert PM (2002) Transglutaminases in disease. Neurochem Int 40:85–103

    Article  CAS  PubMed  Google Scholar 

  16. Ciccocioppo R, Di Sabatino A, Biagi F et al (2003) Gliadin and tissue transglutaminase complexes in normal and coeliac duodenal mucosa. Clin Exp Immunol 134:516–524

    Article  CAS  PubMed  Google Scholar 

  17. Esposito C, Paparo F, Caputo I et al (2003) Expression and enzymatic activity of small intestinal tissue transglutaminase in celiac disease. Am J Gastroenterol 98:1813–1820

    Article  CAS  PubMed  Google Scholar 

  18. Molberg O, Mcadam SN, Körner R et al (1998) Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 4:713–717

    Article  CAS  PubMed  Google Scholar 

  19. Brusco G, Muzi P, Ciccocioppo R et al (1999) Transglutaminase and coeliac disease: endomysial reactivity and small bowel expression. Clin Exp Immunol 118:371–375

    Article  CAS  PubMed  Google Scholar 

  20. Sakly W, Sriha B, Ghedira I et al (2005) Localization of tissue transglutaminase and N (epsilon)-(gamma) -glutamyl lysine in duodenal mucosa during the development of mucosal atrophy in coeliac disease. Virchows Arch 446:613–618

    Article  CAS  PubMed  Google Scholar 

  21. Biagi F, Campanella J, Laforenza U et al (2006) Transglutaminase 2 in the enterocytes is coeliac specific and gluten dependent. Dig Liver Dis 38:652–658

    Article  CAS  PubMed  Google Scholar 

  22. Villanacci V, Not T, Sblattero D et al (2009) Mucosal tissue transglutaminase expression in celiac disease. J Cell Mol Med 13:334–340

    Article  CAS  PubMed  Google Scholar 

  23. Aeschlimann D, Thomazy V (2000) Protein cross-linking in assembly and remodelling of extracellular matrices: the role of transglutaminases. Connect Tissue Res 41:1–27

    Article  CAS  PubMed  Google Scholar 

  24. Hansson T, Ulfgren AK, Lindroos E et al (2002) Transforming growth factor-beta (TGF-beta) and tissue transglutaminase expression in the small intestine in children with coeliac disease. Scand J Immunol 56:530–537

    Article  CAS  PubMed  Google Scholar 

  25. D’Argenio G, Biancone L, Cosenza V et al (1995) Transglutaminases in Crohn's disease. Gut 37:690–695

    Article  PubMed  Google Scholar 

  26. Choi YC, Kim TS, Kim SY (2004) Increase in transglutaminase 2 in idiopathic inflammatory myopathies. Eur Neurol 51:10–14

    Article  CAS  PubMed  Google Scholar 

  27. Wan XH, Lee EH, Koh HJ et al (2002) Enhanced expression of transglutaminase 2 in anterior polar cataracts and its induction by TGF-beta in vitro. Br J Ophthalmol 86:1293–1298

    Article  CAS  PubMed  Google Scholar 

  28. Ientile R, Caccamo D, Griffin M (2007) Tissue transglutaminase and the stress response. Amino Acids 33:385–394

    Article  CAS  PubMed  Google Scholar 

  29. Kim SY, Jeong EJ, Steinert PM (2002) IFN-gamma induces transglutaminase 2 expression in rat small intestinal cells. J Interferon Cytokine Res 22:677–682

    Article  CAS  PubMed  Google Scholar 

  30. Kim SY (2006) Transglutaminase 2 in inflammation. Front Biosci 11:3026–3035

    Article  CAS  PubMed  Google Scholar 

  31. Lee J, Kim YS, Choi DH et al (2004) Transglutaminase 2 induces nuclear factor-kappaB activation via a novel pathway in BV-2 microglia. J Biol Chem 279:53725–53735

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We express our gratitude to Dr. O. Karatysh, Dr. I. Dergacheva, Dr. H. Usau, and Dr. S. Kondrashov for their collaboration and help with the clinical part of the study. The excellent technical assistance of Mrs. S. Klimovich and Mrs. M. Pavlova is also gratefully acknowledged.

Conflict of interest statement

We declare that we have no conflict of interest.

Funding

This work was supported by the Belarusian Republican Foundation for Basic Research (number 20052078).

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Correspondence to Julia Gorgun.

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Gorgun, J., Portyanko, A., Marakhouski, Y. et al. Tissue transglutaminase expression in celiac mucosa: an immunohistochemical study. Virchows Arch 455, 363–373 (2009). https://doi.org/10.1007/s00428-009-0832-9

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