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    Small Intestinal Intraepithelial Gamma/Delta T-Lymphocytes Occur Inversely to Lymphomas in Refractory Celiac Disease


    Jefferson Adams

    Celiac.com 01/20/2009 - Refractory celiac disease is a serious condition that occurs when celiac symptoms and intestinal damage continue even when the patient consumes a gluten-free diet.


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    There are two types of refractory celiac disease (RCD). In RCD type I,  immuno-phenotype of intraepithelial lymphocytes (IELs) are normal and polyclonal, while RCD) type II, is noted for the presence of an abnormal intraepithelial lymphocyte (IEL) population (CD7+ CD3− CD4/8-cytoplasmic CD3+). More than half of people with this condition develop enteropathy-associated T-cell lymphoma (EATL), a rare but virulent form of cancer with high mortality rates.

    A team of doctors recently set out to examine the relationship between lymphoma development and intraepithelial gamma/delta T-lymphocytes in the small intestine of patients with all types of celiac disease, as compared to the general population.

    The team was made up of Wieke H.M. Verbeek, M.D., B. Mary E. von Blomberg, Ph.D., Petra E.T. Scholten, B.Sc., D. Joop Kuik, M.Sc., Chris J.J. Mulder, M.D. Ph.D., and Marco W.J. Schreurs, Ph.D., all from Amsterdam’s VU University Medical Center.

    A certain type of IELs called TCRγ/δ+ IELs may play an important role in repairing mucosa, maintaining homeostasis, and guarding against tumor development. TCRγ/δ+ IELs in the human intestine have recently shown promise in the regulation of uncomplicated celiac disease.

    In the study, the research team wanted to see if patients with RCD II had fewer TCRγ/δ+ IELs than either RDC I, or celiac disease, an thus provide a possible explanation for ongoing mucosal damage and inflammation, and the development of abnormal T cells that tend to morph into EATL.

    The team used a method called multi-parameter flow cytometric immuno-phenotyping on IELs obtained from recent small bowel biopsy specimens from a fairly large, distinct celiac disease and control groups (N = 87).

    Patients with RCD II showed a much lower ratio of TCRγ δ+ IELs compared to either RCD I or celiac disease patients. Whereas, patients with uncomplicated celiac disease showed significantly higher numbers of TCRγ δ+ IELs than were found in the control group. The results showed the relationship between TCRγ δ+ IELs and aberrant IELs to be negative. It is interesting to note that TCRγ δ+ IELs numbers do rise in RCD II patients after effective treatment.

    The negative relationship between TCRγ δ+ and abnormal IELs, together with their known role in regulating uncomplicated celiac disease, suggests that TCRγ δ+ IELs may play a crucial role in helping the body to repair mucosa, maintain homeostasis and possibly even guard against tumor development.

    These cells may serve as important markers, along with the abnormal T cells, to help distinguish between types of celiac disease, and to gage the effectiveness of treatment efforts.

    Am J Gastroenterol 2008;103:3152–3158

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Celiac.com 04/13/2010 - A team of clinicians recently described a case of immune modulation by non-Hodgkin lymphoma in a patient with two primary intestinal T-Cell lymphomas and long-standing celiac disease.
    F. Mühr-Wilkenshoff, M. Friedrich, H. D. Foss, M. Hummel, M. Zeitz, and S. Daum made up the research team. They are variously affiliated with the  Medical Clinic I, Gastroenterology, Rheumatology and Infectious Diseases, and with the Department of Pathology, Charité of the Campus Benjamin Franklin of University Medicine Berlin, Germany.
    About 20–30% of all non-Hodgkin lymphomas (NHLs) are gastrointestinal in nature. Of these gastrointestinal lymphomas, about 20–30% occur in small intestine
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    Doctors resected the lymphoma due to perforation and treated the patient with four courses of IMVP-16. The patient began and maintained a strict gluten-free diet.
    Two years later, the patient appeared with weight loss and a clonally divergent refractory sprue type II with loss of antigen (CD8; T-cell receptor-) expression in intraepithelial lymphocytes.
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    Source:

    Digestion 2010;81:231–234 DOI: 10.1159/000269810

    Jefferson Adams
    Celiac.com 05/19/2010 - Enteropathy-associated T cell lymphoma is a serious complication of celiac disease, and a major cause of mortality in untreated celiac disease.
    One possible trigger for Enteropathy-associated T cell lymphoma development is chronic exposure of intraepithelial lymphocytes (IELs) to strong anti-apoptotic signals, that is, signals that interfere in the normal mortality of the IEL cells. These signals are triggered by IL-15, a cytokine that is over-expressed in the enterocytes of people with celiac disease.
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    The research team was made up of Georgia Malamut, Raja El Machhour, Nicolas Montcuquet, Séverine Martin-Lannerée, Isabelle Dusanter-Fourt, Virginie Verkarre, Jean-Jacques Mention, Gabriel Rahmi, Hiroshi Kiyono, Eric A. Butz, Nicole Brousse, Christophe Cellier, Nadine Cerf-Bensussan, and Bertrand Meresse.
    The are variously affiliated with INSERM U989, the Université Paris Descartes, Faculté de Médecine René Descartes, the Department of Gastroenterology, AP-HP, Hôpital Européen Georges Pompidou, the Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), INSERM U1016, the Department of Pathology, AP-HP, of the Hôpital Necker-Enfants Malades in Paris, with the Division of Mucosal Immunology, Department of Microbiology and Immunology at the Institute of Medical Science at the University of Tokyo in Japan, and the Inflammation Department of AMGEN Inc., in Seattle, Washington, USA.
    Their current findings reveal that the survival signals IL-15 directs to freshly isolated human IELs, and to human IEL cell lines derived from celiac disease patients with type II refractory celiac disease, depend on anti-apoptotic factors Bcl-2 and/or Bcl-xL.
    The signals require IL-15Rβ, Jak3, and STAT5 for proper function, but functioned independently of PI3K, ERK, and STAT3. In support of these findings, the team recorded elevated levels of Bcl-xL, phospho-Jak3, and phospho-STAT5 in IELs from patients with active celiac disease and RCDII.
    Moreover, by incubating patient duodenal biopsies with a fully humanized human IL-15–specific Ab, the team effectively blocked Jak3 and STAT5 phosphorylation.
    Also, treatment with IL-15–specific Ab caused IEL cell mortality, and wiped out the massive IEL build-up in mice over-expressing human IL-15 in their gut epithelium.
    The study marks the first successful mapping of the IL-15–driven survival pathway in human IELs, and demonstrates that IL-15 and its downstream effectors are meaningful therapeutic targets in RCDII.
    These findings will likely help to pave the way for the development of successful immunosuppressive and/or chemotherapeutic treatments that destroy abnormal IELs at the RCDII stage and help to block EATL development, improving outcomes for RCDII patients.
    Source:

    Journal of Clinical Investigation doi:10.1172/JCI41344

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/23/2018 - If you’re looking for a great gluten-free Mexican-style favorite that is sure to be a big hit at dinner or at your next potluck, try these green chili enchiladas with roasted cauliflower. The recipe calls for chicken, but they are just as delicious when made vegetarian using just the roasted cauliflower. Either way, these enchiladas will disappear fast. Roasted cauliflower gives these green chili chicken enchiladas a deep, smokey flavor that diners are sure to love.
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    Roxanne Bracknell
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    Jefferson Adams
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    Premium ingredients, bakeshop delicious recipes, and happy customers were our inspiration from the beginning— and are still the cornerstones of Bakery On Main today. We are a fiercely ethical company that believes in integrity and feels that happiness and wholesome, great tasting food should be harmonious. We strive for that in everything we bake in our dedicated gluten-free facility that is GFCO Certified and SQF Level 3 Certified. We use only natural, NON-GMO Project Verified ingredients and all of our products are certified Kosher Parve, dairy and casein free, and we have recently introduced certified Organic items as well! 
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    Jefferson Adams
    Celiac.com 06/20/2018 - Currently, the only way to manage celiac disease is to eliminate gluten from the diet. That could be set to change as clinical trials begin in Australia for a new vaccine that aims to switch off the immune response to gluten. 
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    Read more at the website for Australia’s University of the Sunshine Coast Clinical Trials Centre.

    Source:
    FoodProcessing.com.au