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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Transamidation of Wheat Flour Inhibits the Response to Gliadin of Intestinal T Cells in Celiac Disease.
Anno di pubblicazione: 2007
Autori: Gianfrani C; Siciliano RA; Facchiano AM; Camarca A; Mazzeo MF; Costantini S; Salvati VM; Maurano F; Mazzarella G; Iaquinto G; Bergamo P; Rossi M.
Affiliazioni autori: Institute of Food Sciences, CNR, Avellino; Department of Pediatrics, University Federico II of Naples, Naples, Italy Gastroenterology and Digestive Endoscopy Service, San G. Moscati Hospital, Avellino, Italy
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.
Lingua abstract: inglese
Pagine da: 780
Pagine a: 789
Numero volume: 133
Numero fascicolo: 3
Indicizzato da: ISI Web of Science (WOS) 
Altre informazioni: 10
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