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Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease.
Gastroenterology. 2007 Sep; 133(3):780-9.G

Abstract

BACKGROUND & AIMS

Celiac disease is characterized by activation of HLA-DQ2/DQ8-restricted intestinal gluten-specific CD4(+) T cells. In particular, gluten becomes a better T-cell antigen following deamidation catalyzed by tissue transglutaminase. To date, the only available therapy is represented by adherence to a gluten-free diet. Here, we examined a new enzyme strategy to preventively abolish gluten activity.

METHODS

Enzyme modifications of the immunodominant alpha-gliadin peptide p56-68 were analyzed by mass spectrometry, and peptide binding to HLA-DQ2 was simulated by modeling studies. Wheat flour was treated with microbial transglutaminase and lysine methyl ester; gliadin was subsequently extracted, digested, and deamidated. Gliadin-specific intestinal T-cell lines (iTCLs) were generated from biopsy specimens from 12 adult patients with celiac disease and challenged in vitro with different antigen preparations.

RESULTS

Tissue transglutaminase-mediated transamidation with lysine or lysine methyl ester of p56-68 or gliadin in alkaline conditions inhibited the interferon gamma expression in iTCLs; also, binding to DQ2 was reduced but not abolished, as suggested by in silico analysis. Lysine methyl ester was particularly effective in abrogating the activity of gliadin. Notably, a block in the response was observed when iTCLs were challenged with gliadin extracted from flour pretreated with microbial transglutaminase and lysine methyl ester.

CONCLUSIONS

Transamidation of wheat flour with a food-grade enzyme and an appropriate amine donor can be used to block the T cell-mediated gliadin activity. Considering the crucial role of adaptive immunity in celiac disease, our findings highlight the potential of the proposed treatment to prevent cereal toxicity.

Authors+Show Affiliations

Institute of Food Sciences, CNR, Avellino, Italy.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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17678925

Citation

Gianfrani, Carmen, et al. "Transamidation of Wheat Flour Inhibits the Response to Gliadin of Intestinal T Cells in Celiac Disease." Gastroenterology, vol. 133, no. 3, 2007, pp. 780-9.
Gianfrani C, Siciliano RA, Facchiano AM, et al. Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology. 2007;133(3):780-9.
Gianfrani, C., Siciliano, R. A., Facchiano, A. M., Camarca, A., Mazzeo, M. F., Costantini, S., Salvati, V. M., Maurano, F., Mazzarella, G., Iaquinto, G., Bergamo, P., & Rossi, M. (2007). Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology, 133(3), 780-9.
Gianfrani C, et al. Transamidation of Wheat Flour Inhibits the Response to Gliadin of Intestinal T Cells in Celiac Disease. Gastroenterology. 2007;133(3):780-9. PubMed PMID: 17678925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. AU - Gianfrani,Carmen, AU - Siciliano,Rosa A, AU - Facchiano,Angelo M, AU - Camarca,Alessandra, AU - Mazzeo,Maria F, AU - Costantini,Susan, AU - Salvati,Virginia M, AU - Maurano,Francesco, AU - Mazzarella,Giuseppe, AU - Iaquinto,Gaetano, AU - Bergamo,Paolo, AU - Rossi,Mauro, Y1 - 2007/06/20/ PY - 2007/03/02/received PY - 2007/05/31/accepted PY - 2007/8/7/pubmed PY - 2007/10/24/medline PY - 2007/8/7/entrez SP - 780 EP - 9 JF - Gastroenterology JO - Gastroenterology VL - 133 IS - 3 N2 - BACKGROUND & AIMS: Celiac disease is characterized by activation of HLA-DQ2/DQ8-restricted intestinal gluten-specific CD4(+) T cells. In particular, gluten becomes a better T-cell antigen following deamidation catalyzed by tissue transglutaminase. To date, the only available therapy is represented by adherence to a gluten-free diet. Here, we examined a new enzyme strategy to preventively abolish gluten activity. METHODS: Enzyme modifications of the immunodominant alpha-gliadin peptide p56-68 were analyzed by mass spectrometry, and peptide binding to HLA-DQ2 was simulated by modeling studies. Wheat flour was treated with microbial transglutaminase and lysine methyl ester; gliadin was subsequently extracted, digested, and deamidated. Gliadin-specific intestinal T-cell lines (iTCLs) were generated from biopsy specimens from 12 adult patients with celiac disease and challenged in vitro with different antigen preparations. RESULTS: Tissue transglutaminase-mediated transamidation with lysine or lysine methyl ester of p56-68 or gliadin in alkaline conditions inhibited the interferon gamma expression in iTCLs; also, binding to DQ2 was reduced but not abolished, as suggested by in silico analysis. Lysine methyl ester was particularly effective in abrogating the activity of gliadin. Notably, a block in the response was observed when iTCLs were challenged with gliadin extracted from flour pretreated with microbial transglutaminase and lysine methyl ester. CONCLUSIONS: Transamidation of wheat flour with a food-grade enzyme and an appropriate amine donor can be used to block the T cell-mediated gliadin activity. Considering the crucial role of adaptive immunity in celiac disease, our findings highlight the potential of the proposed treatment to prevent cereal toxicity. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/17678925/Transamidation_of_wheat_flour_inhibits_the_response_to_gliadin_of_intestinal_T_cells_in_celiac_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)01164-X DB - PRIME DP - Unbound Medicine ER -