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  • Jefferson Adams
    Jefferson Adams
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    Can Vitamin C Reduce Mucosal Immune Inflammatory Response to Gliadin in Celiac Disease Patients?

    Celiac.com 03/28/2012 - A clinical research team wanted to determine if adding ascorbate (vitamin C) to gliadin-stimulated biopsy culture could reduce the mucosal immune response to gliadin in people with celiac disease.

    Photo: CC - articotropical The research team included D. Bernardo, B. Martínez-Abad, S. Vallejo-Diez, E. Montalvillo, V. Benito, B. Anta, L. Fernández-Salazar, A. Blanco-Quirós, J. A. Garrote, and E. Arranz. They are affiliated with the Mucosal Immunology Lab of the Department of Paediatrics & Immunology at Spain's Universidad de Valladolid-CSIC.

    Their quest was fueled by the understanding that the IL-15/NF-κB axis plays a key role in celiac disease. Because ascorbate is known to inhibit effects on NF-κB, the IL-15/NFκB axis looks like a good possible molecular target for reducing gliadin-induced inflammation in celiac disease.

    For their study, the team conducted in vitro gliadin challenges (100 μg/ml) on duodenal biopsy explants from treated patients with celiac disease. Challenges were conducted with and without 20mM ascorbate. As an internal control, the team used an extra tissue explant in basal culture.

    The team then measured secretion levels of nitrites (3h), and IFNγ, TNFα, IFNα, IL-17, IL-13, and IL-6 (24h) on the supernatants. They measured IL-15 using western-blot on whole protein duodenal explants.

    When the team added ascorbate to in vitro culture gliadin-challenged biopsies, they found that the ascorbate blocked secretion of nitrites (p=0.013), IFNγ (p=0.0207), TNFα (p=0.0099), IFNα (p=0.0375), and IL-6 (p=0.0036), as compared with samples from culture that received no ascorbate.

    They also found that the addition of ascorbate reduced cytokine secretion to levels even lower than those observed in basal cultures (IFNγ: p=0.0312; TNFα: p=0.0312; IFNα: p=0.0312; and IL-6: p=0.0078).

    Moreover, the gliadin-challenge triggered IL-15 production in biopsies from treated celiac disease patients, while IL-15 was completely blocked in the cultures that received ascorbate.

    Interestingly, ascorbate completely blocked IL-15 production even in the only treated celiac disease-patient who showed basal IL-15 production.

    From these results, the team concludes that ascorbate reduces the mucosal inflammatory response to gluten in an in vitro biopsy culture. As such, ascorbate might offer supplementary benefits in future celiac disease therapy.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Roy Jamron
    Celiac.com 04/10/2006 - This study looks at innate immune response to gliadin. The innate immune system responds to gliadin inducing zonulin release and increasing intestinal permeability and may be a factor in the onset of celiac disease, but I question if this leads ultimately to the Ag-specific adaptive immune response seen in patients with celiac disease. This innate response fails to explain why one identical twin may have celiac disease and not the other. Both of the twins as well as people not even susceptible to celiac disease would presumably have this same innate response to gliadin. I again urge celiac disease researchers to consider gluten-internalizing bacteria as the necessary trigger for the onset of celiac disease. The presence or absence of such bacteria does indeed offer an explanation as to why one twin gets celiac disease and not the other. Zonulin does not. In the commercial supplement product, Glisodin, the properties of gliadin have, in fact, already been used for the last few years to facilitate the delivery of the antioxidant enzyme superoxide dismutase (SOD) protecting it from digestive acids and getting it through the intestinal mucosa, probably taking advantage of the zonulin effect. Aware of celiac disease, the developer of Glisodin tried to use other peptides as a carrier of SOD, but the only gliadin was effective. Unfortunately, this denies celiacs the benefit of using Glisodin to treat oxidative stress.
    Abstract of Study:


    J Immunol. 2006 Feb 15;176(4):2512-21.
    Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune Response in Celiac Disease.
    Thomas KE, Sapone A, Fasano A, Vogel SN. Department of Microbiology and Immunology.
    Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (celiac disease) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured.
    Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of celiac disease. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with celiac disease.

    Jefferson Adams
    Celiac.com 06/07/2013 - A number of studies have indicated that people with celiac disease have an inadequate response to hepatitis B vaccination. In an effort to better understand the issue, a team of researchers recently set out to assess hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease.
    The research team included F. Zingone, P. Capone, R. Tortora, A. Rispo, F. Morisco, N. Caporaso, N. Imperatore, G. De Stefano, P. Iovino, and C. Ciacci. They are affiliated with the Department of Medicine and Surgery at the University of Salerno in Salerno, Italy.
    To measure the gluten exposure status at the time of vaccination, they compare three groups of patients, along with a control group. In all, the study included 163 celiac patients.
    Group A contained 57 patients exposed to gluten, including patients vaccinated as 12-year-old adolescents, for whom celiac disease diagnosis was established after vaccination. Group B contained 46 patients not exposed to gluten, including patients vaccinated as 12-year-old adolescents and on a gluten-free diet at the time of vaccination. Group C was composed of 60 infants, including those vaccinated at birth. Group D included 48 healthy, vaccinated, non-celiac subjects. The researchers then compared the response of celiac patients to hepatitis B vaccination with the response by healthy subjects. They found that 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D showed inadequate response to hepatitis B immunization.
    Overall, group A versus group D, P less than 0.001; group B versus group D, P = 0.002; group C versus group D, P = 0.001, while they found no significant difference for group A versus group B and group A versus group C.
    This study suggests that gluten exposure does not influence the response to hepatitis B immunization, and that the human leukocyte antigen likely plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients.
    Source:
    Clin Vaccine Immunol. 2013 May;20(5):660-2. doi: 10.1128/CVI.00729-12. Epub 2013 Feb 27.

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