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    Jefferson Adams
    Jefferson Adams

    Gluten Peptide Research Advancing Immunotherapy for Celiac Disease

    Reviewed and edited by a celiac disease expert.

    Celiac.com 04/24/2009 - Currently, one of the more promising areas of celiac disease research looks to be in peptide-based therapies. One of the keys to creating an effective peptide-based therapy for celiac disease lies in identifying the gluten peptides that trigger intestinal T cell responses when people with celiac disease consume wheat, rye, or barley.

    A team of Italian researchers recently set out to do just that. The team was made up of A. Camarca, R.P. Anderson, G. Mamone, O. Fierro , A. Facchiano, S. Costantini, D. Zanzi, J. Sidney, S. Auricchio, A. Sette, R. Troncone, and C. Gianfrani. Their efforts were supported by the Institute of Food Sciences-National Research Council, Avellino, Italy. Their research carries strong implications for a Open Original Shared Link.

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    Presently, several gluten peptides are known to be active in celiac disease. The identification of additional gluten peptides eliciting intestinal T cell responses is critical for designing a successful peptide-based immunotherapy for celiac disease.

    In their study, the research team assessed the recognition profile of gluten immunogenic peptides in adult HLA-DQ2(+) celiac patients. They did so by creating several lines of polyclonal, gliadin-reactive T cells from jejunal mucosa. They then tested for both proliferation and IFN-gamma production in reaction to 21 peptides from wheat glutenins and alpha-, gamma-, and omega-gliadins.  They then conducted a magnitude analysis of the IFN-gamma responses to determine the spectrum of individual peptide activity, and to rank them accordingly.

    Notably, 12 of the 14 patients responded to a different array of peptides. All alpha-gliadin stimulatory peptides mapped the 57-89 N-terminal region, thus affirming the importance of the known polyepitope 33-mer, although  only 50% of subjects recognized 33-mer.

    By contrast, 11 of 14 celiac subjects, nearly 80%, responded to gamma-gliadin peptides. A 17-mer variant of 33-mer, QLQPFPQPQLPYPQPQP, posessing only a single copy of DQ2-alpha-I and DQ2-alpha-II epitopes, displayed the same potency as 33-mer in triggering intestinal T cell responses.

    One particular peptide from omega-gliadin, QPQQPFPQPQQPFPWQP, though structurally related to the alpha-gliadin 17-mer, is a separate epitope and activated in 5 out of 14 subjects.

    The team's data reveal that intestinal T cells respond to a wide array of peptides, and that this heterogeneity  emphasizes the relevance of gamma- and omega-gliadin peptides in celiac disease pathogenesis. Their findings indicate that, in DQ2(+) celiac patients, the most active gluten peptides are alpha-gliadin (57-73), gamma-gliadin (139-153), and omega-gliadin (102-118).


    J Immunol. 2009 Apr 1;182(7):4158-66.



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    Guest Gerald Jones

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    Way too technical. The only people who can understand that is the people doing the research.

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    Guest Fred Martin

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    Good article. From nearly nearly everything I've read, enzymes look very promising for treating celiac disease.

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  • About Me

    Jefferson Adams

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University. His articles, essays, poems, stories and book reviews have appeared in numerous magazines, journals, and websites, including North American Project, Antioch Review, Caliban, Mississippi Review, Slate, and more. He is the author of more than 2,500 articles on celiac disease. His university coursework includes studies in science, scientific methodology, biology, anatomy, physiology, medicine, logic, and advanced research. He previously devised health and medical content for Colgate, Dove, Pfizer, Sharecare, Walgreens, and more. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of numerous books, including "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

    >VIEW ALL ARTICLES BY JEFFERSON ADAMS

     


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