Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation
Carroccio, A.; Di Prima, L.; Noto, D,; Fayer, F.; Ambrosiano, G.; Villanacci, V.; Lammers, K.; Lafiandra, D.; De Ambrogio, E.; Iacono, G.; Pogna N.
Digestive Liver Disease
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Background: Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity. Aim: Evaluation of the bread wheat line C173 with a modified gluten composition for its effects on the in vitro-grown duodenal mucosa of CD patients in terms of histological modifications and production of cytokines and anti-tissue-transglutaminase (anti-tTG) antibodies. Methods: In vitro-grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadins plus glutenin subunits encoded by the short arms of chromosomes 1D and 6A, analyzed for their morphology and production of IFN- ?, IL-2, IL-10 and anti-tTG antibodies and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore. Results: Duodenal mucosa biopsies exposed to prolamins from C173 and San Pastore released higher amounts of IFN-?, IL-2, IL-10 and anti-tTG antibodies in the culture medium than untreated controls. However, the line C173 differed from cv. San Pastore as it did not produce negative effects on enterocyte height, suggesting that manipulating prolamin composition can affect innate immune responses of CD mucosa to wheat gluten. Conclusions: Our data demonstrated that this gliadin-deficient wheat has a lower direct toxicity but activates an immunologic reaction of the duodenal mucosa like that of the common wheat species. An association of different new experimental approaches together with the consumption of a “less toxic” wheat could help reach the objective of finding an alternative to GFD.