Mechanisms of epithelial translocation of the α2-gIiadin-33mer in coeliac sprue

Schumann, M.; Richter, J. F.; Wedell, I.; Moos, V.; Zimmermann-Kordmann, M.; Schneider, T.; Daum, S.; Zeitz, M.; Fromm, M.; Schulzke, J. D.
June 2008
Gut;Jun2008, Vol. 57 Issue 6, p747
Academic Journal
Background and aims: The α2-gliadin-33mer has been shown to be important in the pathogenesis of coeliac disease. We aimed to study mechanisms of its epithelial translocation and processing in respect to transcytotic and paracellular pathways. Methods: Transepithelial passage of a fluorescence-labelled α2-gIiadin-33mer was studied in Caco-2 cells by using reverse-phase high-performance liquid chromatography, mass spectrometry, confocal laser scanning microscopy (LSM) and fluorescence activated cell sorting (FACS). Endocytosis mechanisms were characterised with rab-GFP constructs transiently transfected into Caco-2 cells and in human duodenal biopsy specimens. Results: The α2-gliadin-33mer dose-dependently crossed the epithelial barrier in the apical-to-basal direction. Degradation analysis revealed translocation of the 33mer polypeptide in the uncleaved as well as in the degraded form. Transcellular passage was identified by confocal LSM, inhibitor experiments and FACS. Rab5 but not rab4 or rab7 vesicles were shown to be part of the transcytotic pathway. After pre-incubation with interferon-γ, translocation of the 33mer was increased by 40%. In mucosal biopsies of the duodenum, epithelial 33mer uptake was significantly higher in untreated coeliac disease patients than in healthy controls or coeliac disease patients on a gluten-free diet. Conclusion: Epithelial translocation of the α2-gliadin-33mer occurs by transcytosis after partial degradation through a rab5 endocytosis compartment and is regulated by interferon-γ. Uptake of the 33mer is higher in untreated coeliac disease than in controls and coeliac disease patients on a gluten-free diet.


Related Articles

  • Absence of urinary opioid peptides in children with autism. Cass, H.; Gringras, P.; March, J.; McKendrick, I.; O'Hare, A. E.; Owen, L.; PoIIin, C. // Archives of Disease in Childhood;Sep2008, Vol. 93 Issue 9, p745 

    Objective: It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to...

  • Identification and In Vitro Reactivity of Celiac Immunoactive Peptides in an Apparent Gluten-Free Beer. Real, Ana; Comino, Isabel; Moreno, Mª de Lourdes; López-Casado, Miguel Ángel; Lorite, Pedro; Torres, Mª Isabel; Cebolla, Ángel; Sousa, Carolina // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific...

  • My very, very, very good life -- really! Schwarz, Meryl // GIG Newsletter;Fall2008, Vol. 31 Issue 4, p38 

    A personal narrative is presented which explores the author's experience of being diagnosed with celiac disease and being able to manage it with a gluten-free diet and change of lifestyle.

  • The enriching gluten-free journey. Wey, Steve // GIG Newsletter;Fall2008, Vol. 31 Issue 4, p44 

    A personal narrative is presented which explores the author's experience of coping with celiac disease and relying on a gluten-free diet.

  • Industry Expert: The Gluten-Free Diet 101. Case, Shelley // Snack Food & Wholesale Bakery;May2012, Vol. 101 Issue 5, p8 

    In this article, the author presents information about the gluten-free diet and gluten free specialty products in context of the National Celiac Awareness Month in May.

  • Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease. Vahedi, Kouroche; Mascart, Françoise; Mary, Jean-Yves; Laberenne, Jean-Eric; Bouhnik, Yoram; Morin, Marie-Christine; Ocmant, Annick; Velly, Christine; Colombel, Jean-Frédéric; Matuchansky, Claude // American Journal of Gastroenterology;May2003, Vol. 98 Issue 5, p1079 

    : ObjectiveStrict lifelong compliance to a gluten-free diet (GFD) minimizes the long-term risk of mortality, especially from lymphoma, in adult celiac disease (CD). Although serum IgA antitransglutaminase (IgA-tTG-ab), like antiendomysium (IgA-EMA) antibodies, are sensitive and specific...

  • A Primer on Gluten for Celiac Awareness Month. Neugent, Brenda // Diabetes Health Professional;Oct/Nov2014, Vol. 23 Issue 5, p29 

    No abstract available.

  • Gluten-free diet benefits coeliac disease· patients.  // Pulse;10/24/2012, Vol. 72 Issue 35, p17 

    The article offers information on a research conducted by the researchers of Sweden and reports that gluten-free diet improves the multiple outcomes of celiac disease patients.

  • Quinoa Well Tolerated in Patients With Celiac Disease.  // Today's Dietitian;Apr2014, Vol. 16 Issue 4, p62 

    No abstract available.


Read the Article


Sign out of this library

Other Topics