All Title Author
Keywords Abstract


Novel Therapeutic/Integrative Approaches for Celiac Disease and Dermatitis Herpetiformis

DOI: 10.1155/2012/959061

Full-Text   Cite this paper   Add to My Lib

Abstract:

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Gluten is a protein component in wheat and other cereals like rye and barley. At present, the only available treatment is a strict gluten-free diet. Recent advances have increased our understanding of the molecular basis for this disorder. Last decade has seen new scientific developments in this disease and led to the formulation of new concepts of pathophysiology that offer possible targets for new treatments or interventions integrative to the gluten-free diet. 1. Introduction Celiac disease (CD) is an immune-mediated chronic enteropathy with a wide range of presenting manifestations of variable severity. It is triggered by the ingestion of gliadin fraction of wheat gluten and similar alcohol-soluble proteins (prolamins) of barley and rye in genetically susceptible subjects with subsequent immune reaction leading to small bowel inflammation and normalization of the villous architecture in response to a gluten-free diet (GFD). CD not only affects the gut, but it is a systemic disease that may cause injury to the skin (dermatitis herpetiformis, the topic of this special issue), liver, joints, brain, heart, and other organs. It is a complex genetic disorder, and human leukocyte antigen (HLA) status appears to be the strongest genetic determinant of risk for celiac autoimmunity. There is a propensity for individuals with CD to carry specific HLA class II alleles, which has been estimated to account for up to 40% of the genetic load [1]. In affected individuals, 95% have either DQ2 (HLA-DQA1*05-DQB1*02) or DQ8 (HLADQA1*03-DQB1*0302), in comparison with the general population in which 39.5% have either DQ2 or DQ8 [2]. It is the interplay between genes (both HLA and non-HLA associated) and environment (i.e., gluten) that leads to the intestinal damage typical of the disease [3]. Under physiological circumstances, this interplay is prevented by competent intercellular tight junctions (TJs), structures that limit the passage of macromolecules (including gluten) across the intestinal epithelial barrier. Recent evidence suggests that the gluten-induced upregulation of zonulin, a recently described intestinal peptide involved in TJ regulation, is responsible, at least in part, for the aberrant increase in gut permeability characteristic of the early phase of CD [4] and the subsequent abnormal passage of gluten into the lamina propria. Here, the protein is deamidated by tissue transglutaminase and is then recognized by HLA-DQ2/DQ8

References

[1]  S. Bevan, S. Popat, C. P. Braegger et al., “Contribution of the MHC region to the familial risk of coeliac disease,” Journal of Medical Genetics, vol. 36, no. 9, pp. 687–690, 1999.
[2]  L. H?gberg, K. F?lth-Magnusson, E. Grodzinsky, and L. Stenhammar, “Familial prevalence of coeliac disease: a twenty-year follow-up study,” Scandinavian Journal of Gastroenterology, vol. 38, no. 1, pp. 61–65, 2003.
[3]  D. Schuppan, “Current concepts of celiac disease pathogenesis,” Gastroenterology, vol. 119, no. 1, pp. 234–242, 2000.
[4]  A. Fasano, T. Not, W. Wang et al., “Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease,” The Lancet, vol. 355, no. 9214, pp. 1518–1519, 2000.
[5]  S. Byrne, Z. Cooper, and C. Fairburn, “Weight maintenance and relapse in obesity: a qualitative study,” International Journal of Obesity, vol. 27, no. 8, pp. 955–962, 2003.
[6]  C. Catassi, E. Fabiani, G. Iacono et al., “A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease,” American Journal of Clinical Nutrition, vol. 85, no. 1, pp. 160–166, 2007.
[7]  S. Accomando, A. Picarelli, I. DeVitis et al., “A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease,” The American Journal of Clinical Nutrition, vol. 85, no. 1, pp. 160–166, 2007.
[8]  A. Lanzini, F. Lanzarotto, A. Mora, S. Bertolazzi, F. Benini, and C. Ricci, “Small intestinal recovery is often incomplete in serum-negative celiacs during gluten free-diet,” Gastroenterology, vol. 132, article A109, 2007.
[9]  P. Collin, L. Thorell, K. Kaukinen, and M. M?ki, “The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease?” Alimentary Pharmacology and Therapeutics, vol. 19, no. 12, pp. 1277–1283, 2004.
[10]  C. Hischenhuber, R. Crevel, B. Jarry et al., “Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease,” Alimentary Pharmacology and Therapeutics, vol. 23, no. 5, pp. 559–575, 2006.
[11]  M. Per?aho, K. Kaukinen, K. Paasikivi et al., “Wheat-starch-based gluten-free products in the treatment of newly detected coeliac disease: prospective and randomized study,” Alimentary Pharmacology and Therapeutics, vol. 17, no. 4, pp. 587–594, 2003.
[12]  L. Maiuri, C. Ciacci, I. Ricciardelli et al., “Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease,” The Lancet, vol. 362, no. 9377, pp. 30–37, 2003.
[13]  J. L. Madara and J. S. Trier, “Stuctural abnormalities of jejunal epithelial cell membranes in celiac sprue,” Laboratory Investigation, vol. 43, no. 3, pp. 254–261, 1980.
[14]  J. D. Schulzke, C. J. Bentzel, I. Schulzke, E. O. Riecken, and M. Fromm, “Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue,” Pediatric Research, vol. 43, no. 4 I, pp. 435–441, 1998.
[15]  M. G. Clemente, S. De Virgiliis, J. S. Kang et al., “Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function,” Gut, vol. 52, no. 2, pp. 218–223, 2003.
[16]  S. Drago, R. El Asmar, M. Di Pierro et al., “Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines,” Scandinavian Journal of Gastroenterology, vol. 41, no. 4, pp. 408–419, 2006.
[17]  W. Wang, S. Uzzau, S. E. Goldblum, and A. Fasano, “Human zonulin, a potential modulator of intestinal tight junctions,” Journal of Cell Science, vol. 113, no. 24, pp. 4435–4440, 2000.
[18]  A. Tripathi, K. M. Lammers, S. Goldblum et al., “Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 39, pp. 16799–16804, 2009.
[19]  A. Fasano, T. Not, W. Wang et al., “Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease,” The Lancet, vol. 355, no. 9214, pp. 1518–1519, 2000.
[20]  L. Leach and J. A. Firth, “Structure and permeability of human placental microvasculature,” Microscopy Research and Technique, vol. 38, pp. 137–144, 1997.
[21]  K. L. Madsen, S. A. Lewis, M. M. Tavernini, J. Hibbard, and R. N. Fedorak, “Interleukin 10 prevents cytokine-induced disruption of T84 monolayer barrier integrity and limits chloride secretion,” Gastroenterology, vol. 113, no. 1, pp. 151–159, 1997.
[22]  M. Schumann, D. Günzel, N. Buergel et al., “Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease,” Gut, vol. 61, pp. 220–228, 2012.
[23]  C. Lebreton, S. Ménard, J. Abed et al., “Interactions among secretory immunogloblulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides,” Gastroenterology, vol. 143, no. 3, pp. 698–707, 2012.
[24]  H. Arentz-Hansen, S. N. Mcadam, O. Molberg et al., “Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues,” Gastroenterology, vol. 123, no. 3, pp. 803–809, 2002.
[25]  W. Vader, Y. Kooy, P. Van Veelen et al., “The Gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides,” Gastroenterology, vol. 122, no. 7, pp. 1729–1737, 2002.
[26]  L. W. Vader, A. de Ru, Y. van der Wal et al., “Specificity of tissue transglutaminase explains cereal toxicity in celiac disease,” Journal of Experimental Medicine, vol. 195, no. 5, pp. 643–649, 2002.
[27]  L. Shan, ?. Molberg, I. Parrot et al., “Structural basis for gluten intolerance in Celiac Sprue,” Science, vol. 297, no. 5590, pp. 2275–2279, 2002.
[28]  S. W. Qiao, E. Bergseng, ?. Molberg et al., “Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion,” Journal of Immunology, vol. 173, no. 3, pp. 1757–1762, 2004.
[29]  E. M. Nilsen, F. L. Jahnsen, K. E. A. Lundin et al., “Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease,” Gastroenterology, vol. 115, no. 3, pp. 551–563, 1998.
[30]  A. Fasano, “Surprise from celiac Disease,” Scientific American, vol. 301, no. 2, pp. 54–61, 2009.
[31]  I. Aziz, K. E. Evans, V. Papageorgiou, and D. S. Sanders, “Are patients with coeliac disease seeking alternative therapies to a gluten-free diet?” Journal of Gastrointestinal and Liver Diseases, vol. 20, no. 1, pp. 27–31, 2011.
[32]  M. Siegel, M. E. Garber, A. G. Spencer et al., “Safety, tolerability, and activity of ALV003: results from two phase 1 single, escalating-dose clinical trials,” Digestive Diseases and Sciences, vol. 57, pp. 440–450, 2012.
[33]  R. Di Cagno, M. De Angelis, S. Auricchio et al., “Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients,” Applied and Environmental Microbiology, vol. 70, no. 2, pp. 1088–1096, 2004.
[34]  M. Piacentini and V. Colizzi, “Tissue transglutaminase: apoptosis versus autoimmunity,” Immunology Today, vol. 20, no. 3, pp. 130–134, 1999.
[35]  D. Schuppan and W. Dieterich, “A molecular warhead and its target: tissue transglutaminase and celiac sprue,” Chemistry and Biology, vol. 10, no. 3, pp. 199–201, 2003.
[36]  A. Fasano and T. Shea-Donohue, “Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases,” Nature Clinical Practice Gastroenterology and Hepatology, vol. 2, no. 9, pp. 416–422, 2005.
[37]  S. O. Ukabam and B. T. Cooper, “Small intestinal permeability as an indicator of jejunal mucosal recovery in patients with celiac sprue on a gluten-free diet,” Journal of Clinical Gastroenterology, vol. 7, no. 3, pp. 232–236, 1985.
[38]  T. Watts, I. Berti, A. Sapone et al., “Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 8, pp. 2916–2921, 2005.
[39]  B. M. Paterson, K. M. Lammers, M. C. Arrieta, A. Fasano, and J. B. Meddings, “The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study,” Alimentary Pharmacology and Therapeutics, vol. 26, no. 5, pp. 757–766, 2007.
[40]  S. Gopalakrishnan, M. Durai, K. Kitchens et al., “Larazotide acetate regulates epithelial tight junctions in vitro and in vivo,” Peptides, vol. 35, pp. 86–94, 2012.
[41]  S. Gopalakrishnan, A. Tripathi, A. P. Tamiz, S. S. Alkan, and N. B. Pandey, “Larazotide acetate promotes tight junction assembly in epithelial cells,” Peptides, vol. 35, pp. 95–101, 2012.
[42]  L. C. Pérez, G. C. de Villasante, A. C. Ruiz, and F. León, “Non-dietary therapeutic clinical trials in coeliac disease,” European Journal of Internal Medicine, vol. 23, pp. 9–14, 2012.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal