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    Altered Gluten Proteins Still Trigger Intestinal T-cell Responses in Celiacs


    Scott Adams

    Gastroenterology. 2003 Aug;125(2):337-344.


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    Celiac.com 08/07/2003 - This studys aim was to determine the feasibility of altering gluten proteins to make them harmless to those with celiac disease. Unfortunately the altered protein still produced a toxic T-cell reaction in almost half of the patients studied. Here is the abstract:

    Intestinal T-cell responses to high-molecular-weight glutenins in celiac disease.

    Molberg O, Solheim Flaete N, Jensen T, Lundin KE, Arentz-Hansen H, Anderson OD, Kjersti Uhlen A, Sollid LM.

    BACKGROUND & AIMS: The chronic, small intestinal inflammation that defines celiac disease is initiated by a HLA-DQ2 restricted T-cell response to ingested gluten peptides after their in vivo examination by tissue transglutaminase (TG2). To date, celiac disease can only be treated by a lifelong abstinence from foods that contain wheat, rye, or barley; better therapeutic options are hence needed. An attractive target would be to identify nontoxic wheat cultivars or components thereof with intact baking qualities. Because these qualities are mainly determined by the high molecular weight (HMW) glutenin proteins of gluten, it is critical to know if these proteins are toxic or, more specifically, if they will trigger the activation of T cells in the celiac lesion.

    METHODS: Different, highly purified HMW glutenins were isolated from wheat cultivars or expressed as recombinant proteins. The proteins were first tested for recognition by a large panel of gluten-specific T-cell lines established from celiac lesions and then applied during ex vivo challenges of celiac biopsies to allow for a direct identification of HMW specific T cells.

    RESULTS: Intestinal T-cell responses to TG2-deamidated HMW glutenins but not the corresponding native proteins were detectable in 9 of the 22 adult and childhood celiac disease patients tested.

    CONCLUSIONS: T cells within celiac lesions frequently recognize deamidated HMW glutenin proteins. This finding questions the possibility of implementing these proteins in novel food items destined to be nontoxic for celiac disease patients.

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    In 1994 I was diagnosed with celiac disease, which led me to create Celiac.com in 1995. I created this site for a single purpose: To help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives. Celiac.com was the first site on the Internet dedicated solely to celiac disease. In 1998 I founded The Gluten-Free Mall, Your Special Diet Superstore!, and I am the co-author of the book Cereal Killers, and founder and publisher of Journal of Gluten Sensitivity.

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    Scott Adams
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    Kamran Rostami, M.D., Ph.D. Department of Medicine, Gloucestershire Royal Hospital Gloucester, UK
    Kenneth Fine, M.D. The Intestinal Health Institute, Dallas, Texas, USA
    We have read with interest the article by Kappler et al recently published in your journal (1) and feel several issues deserve mention. This article is very timely in light of the growing worldwide awareness of immunologic sensitivity to dietary gluten and celiac disease, as well as appreciation of its high prevalence; these facts are driving the need for more widely available, low cost, non-invasive screening tests. Stool testing for these disorders holds great promise for screening because it does not require any invasion of body tissues, is of relatively low cost, and could be widely available combining medical care delivery of such tests with home testing.
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    References:
    1. Kappler M, Krauss-Etschmann S, Diehl V, Zeilhofer H, Koletzko S. Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for celiac disease in children: validation study. BMJ. 2006 January 28; 332(7535): 213-14.
    2. Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol. 1999 Apr;94(4):888-94.
    3. Ferguson A, Arranz E, OMahony S. Clinical and pathological spectrum of celiac disease--active, silent, latent, potential. Gut. 1993 Feb;34(2):150-1.
    4. Arranz E, Ferguson A. Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and potential celiac disease. Adv Exp Med Biol. 1995;371B:1345-8.

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