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Unexpected role of surface transglutaminase type II in celiac disease.
Gastroenterology. 2005 Nov; 129(5):1400-13.G

Abstract

BACKGROUND & AIMS

In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach.

METHODS

Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, palpha-9, and deamidated palpha-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis.

RESULTS

The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells.

CONCLUSIONS

These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases.

Authors+Show Affiliations

Institute of Child Health, University College London, London, England.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16285941

Citation

Maiuri, Luigi, et al. "Unexpected Role of Surface Transglutaminase Type II in Celiac Disease." Gastroenterology, vol. 129, no. 5, 2005, pp. 1400-13.
Maiuri L, Ciacci C, Ricciardelli I, et al. Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology. 2005;129(5):1400-13.
Maiuri, L., Ciacci, C., Ricciardelli, I., Vacca, L., Raia, V., Rispo, A., Griffin, M., Issekutz, T., Quaratino, S., & Londei, M. (2005). Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology, 129(5), 1400-13.
Maiuri L, et al. Unexpected Role of Surface Transglutaminase Type II in Celiac Disease. Gastroenterology. 2005;129(5):1400-13. PubMed PMID: 16285941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unexpected role of surface transglutaminase type II in celiac disease. AU - Maiuri,Luigi, AU - Ciacci,Carolina, AU - Ricciardelli,Ida, AU - Vacca,Loredana, AU - Raia,Valeria, AU - Rispo,Antonio, AU - Griffin,Martin, AU - Issekutz,Thomas, AU - Quaratino,Sonia, AU - Londei,Marco, PY - 2004/07/18/received PY - 2005/07/14/accepted PY - 2005/11/16/pubmed PY - 2006/1/13/medline PY - 2005/11/16/entrez SP - 1400 EP - 13 JF - Gastroenterology JO - Gastroenterology VL - 129 IS - 5 N2 - BACKGROUND & AIMS: In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. METHODS: Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, palpha-9, and deamidated palpha-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. RESULTS: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. CONCLUSIONS: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/16285941/Unexpected_role_of_surface_transglutaminase_type_II_in_celiac_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(05)01564-7 DB - PRIME DP - Unbound Medicine ER -