International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: Editor-in-chief: Samasca Gabriel
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International Journal of Celiac Disease. 2013, 1(1), 9-13
DOI: 10.12691/ijcd-1-1-5
Open AccessEditorial

Coeliac Disease: From Triggering Factors to Treatment

Erna Sziksz1, 2, , Péter Vörös2, Gábor Veres2, Andrea Fekete2, 3 and Ádám Vannay1, 2

1Research Group for Pediatrics and Nephrology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

2First Department of Pediatrics, Semmelweis University, Budapest, Hungary

3“Momentum” Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

Pub. Date: December 12, 2013

Cite this paper:
Erna Sziksz, Péter Vörös, Gábor Veres, Andrea Fekete and Ádám Vannay. Coeliac Disease: From Triggering Factors to Treatment. International Journal of Celiac Disease. 2013; 1(1):9-13. doi: 10.12691/ijcd-1-1-5


Coeliac disease (CD) or gluten sensitive enteropathy is one of the most common inflammatory diseases of the small intestine with estimated prevalence of 1% in the population. Its incidence is increasing and seems to be higher than expected in the pediatric population associated with unfavorable impact on the quality of life. The aim of the present review is to highlight the main triggering factors leading to the development of CD and its pathomechanism with a special outlook to the recent therapeutic approaches.

coeliac disease triggering factors pathomechanism therapy

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[1]  Setty, M., Hormaza, L., Guandalini, S. Celiac disease: risk assessment, diagnosis, and monitoring. Molecular diagnosis & therapy, 12 (5):289-98. 2008.
[2]  Green, P.H., Cellier, C. Celiac disease. The New England journal of medicine, 357 (17):1731-43. 2007.
[3]  Makovicky, P., Rimarova, K., Boor, A., Makovicky, P., Vodicka, P., Samasca, G., Kruzliak, P. Correlation between antibodies and histology in celiac disease: incidence of celiac disease is higher than expected in the pediatric population. Molecular medicine reports, 8 (4):1079-83. 2013.
[4]  Rubio-Tapia, A., Murray, J.A. Classification and management of refractory coeliac disease. Gut, 59 (4):547-57. 2010
[5]  Baldassarre, M., Laneve, A.M., Grosso, R., Laforgia, N. Celiac disease: pathogenesis and novel therapeutic strategies. Endocrine, metabolic & immune disorders drug targets, 8 (3):152-8. 2008.
[6]  Jabri, B., Sollid, L.M. Mechanisms of disease: immunopathogenesis of celiac disease. Nature clinical practice. Gastroenterology & hepatology, 3 (9): 516-25. 2006.
[7]  Rostom, A., Dube, C., Cranney, A., Saloojee, N., Sy, R., Garritty, C., Sampson, M., Zhang, L., Yazdi, F., Mamaladze, V., Pan, I., MacNeil, J., Mack, D., Patel, D., Moher, D. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology, 128 (4 Suppl 1):S38-46. 2005.
[8]  Lauret, E., Rodrigo, L. Celiac disease and autoimmune-associated conditions. BioMed research international, 2013:127589. 2013.
[9]  Schuppan, D., Dennis, M.D., Kelly, C.P. Celiac disease: epidemiology, pathogenesis, diagnosis, and nutritional management. Nutrition in clinical care : an official publication of Tufts University, 8 (2):54-69. 2005.
[10]  Karell, K., Louka, A.S., Moodie, S.J., Ascher, H., Clot, F., Greco, L., Ciclitira, P.J., Sollid, L.M., Partanen, J., European Genetics Cluster on Celiac, D. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Human immunology, 64 (4):469-77. 2003.
[11]  Shan, L., Molberg, O., Parrot, I., Hausch, F., Filiz, F., Gray, G.M., Sollid, L.M., Khosla, C. Structural basis for gluten intolerance in celiac sprue. Science, 297 (5590):2275-9. 2002
[12]  Caccamo, D., Curro, M., Ientile, R. Potential of transglutaminase 2 as a therapeutic target. Expert opinion on therapeutic targets, 14 (9):989-1003. 2010.
[13]  Sollid, L.M. Coeliac disease: dissecting a complex inflammatory disorder. Nature reviews. Immunology, 2 (9):647-55. 2002.
[14]  Lewis, K., McKay, D.M. Metabolic stress evokes decreases in epithelial barrier function. Annals of the New York Academy of Sciences, 1165:327-37. 2009.
[15]  Szaflarska-Poplawska, A., Siomek, A., Czerwionka-Szaflarska, M., Gackowski, D., Rozalski, R., Guz, J., Szpila, A., Zarakowska, E., Olinski, R. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 19 (8):1960-5. 2010.
[16]  Schuppan, D., Junker, Y., Barisani, D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology, 137 (6):1912-33. 2009.
[17]  Szebeni, B., Veres, G., Dezsofi, A., Rusai, K., Vannay, A., Bokodi, G., Vasarhelyi, B., Korponay-Szabo, I.R., Tulassay, T., Arato, A. Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in coeliac disease. Journal of pediatric gastroenterology and nutrition, 45 (2):187-93. 2007.
[18]  Iltanen, S., Rantala, I., Laippala, P., Holm, K., Partanen, J., Maki, M. Expression of HSP-65 in jejunal epithelial cells in patients clinically suspected of coeliac disease. Autoimmunity, 31 (2):125-32. 1999.
[19]  Sziksz, E., Veres, G., Vannay, A., Prokai, A., Gal, K., Onody, A., Korponay-Szabo, I.R., Reusz, G., Szabo, A., Tulassay, T., Arato, A., Szebeni, B. Increased heat shock protein 72 expression in celiac disease. Journal of pediatric gastroenterology and nutrition, 51 (5):573-8. 2010.
[20]  Li, Z., Menoret, A., Srivastava, P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Current opinion in immunology, 14 (1):45-51. 2002.
[21]  Takeda, K., Kaisho, T., Akira, S. Toll-like receptors. Annual review of immunology, 21:335-76. 2003.
[22]  Jeon, M.K., Klaus, C., Kaemmerer, E., Gassler, N. Intestinal barrier: Molecular pathways and modifiers. World journal of gastrointestinal pathophysiology, 4 (4):94-99. 2013.
[23]  Laukoetter, M.G., Bruewer, M., Nusrat, A. Regulation of the intestinal epithelial barrier by the apical junctional complex. Current opinion in gastroenterology, 22 (2):85-9. 2006.
[24]  Fasano, A. Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences, 1258:25-33. 2012.
[25]  Tripathi, A., Lammers, K.M., Goldblum, S., Shea-Donohue, T., Netzel-Arnett, S., Buzza, M.S., Antalis, T.M., Vogel, S.N., Zhao, A., Yang, S., Arrietta, M.C., Meddings, J.B., Fasano, A. 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, 106 (39):16799-804. 2009.
[26]  Catalioto, R.M., Maggi, C.A., Giuliani, S. Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions. Current medicinal chemistry, 18 (3):398-426. 2011.
[27]  Niecknig, H., Tug, S., Reyes, B.D., Kirsch, M., Fandrey, J., Berchner-Pfannschmidt, U. Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase 2 under mild hypoxia. Free radical research, 46 (6):705-17. 2012.
[28]  Diosdado, B., van Oort, E., Wijmenga, C. "Coelionomics": towards understanding the molecular pathology of coeliac disease. Clinical chemistry and laboratory medicine: CCLM / FESCC, 43 (7):685-95. 2005.
[29]  Vasseur, S., Afzal, S., Tardivel-Lacombe, J., Park, D.S., Iovanna, J.L., Mak, T.W. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proceedings of the National Academy of Sciences of the United States of America, 106 (4):1111-6. 2009.
[30]  Voros, P., Sziksz, E., Himer, L., Onody, A., Pap, D., Frivolt, K., Szebeni, B., Lippai, R., Gyorffy, H., Fekete, A., Brandt, F., Molnar, K., Veres, G., Arato, A., Tulassay, T., Vannay, A. Expression of PARK7 is increased in celiac disease. Virchows Archiv: an international journal of pathology, 463 (3):401-8. 2013.
[31]  Vannay, A., Sziksz, E., Prokai, A., Veres, G., Molnar, K., Szakal, D.N., Onody, A., Korponay-Szabo, I.R., Szabo, A., Tulassay, T., Arato, A., Szebeni, B. Increased expression of hypoxia-inducible factor 1alpha in coeliac disease. Pediatric research, 68 (2):118-22. 2010.
[32]  Lee, A., Newman, J.M. Celiac diet: its impact on quality of life. Journal of the American Dietetic Association, 103 (11):1533-5. 2003.
[33]  Rashtak, S., Murray, J.A. Review article: coeliac disease, new approaches to therapy. Alimentary pharmacology & therapeutics, 35 (7):768-81. 2012.
[34]  van den Broeck, H.C., van Herpen, T.W., Schuit, C., Salentijn, E.M., Dekking, L., Bosch, D., Hamer, R.J., Smulders, M.J., Gilissen, L.J., van der Meer, I.M. Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines. BMC plant biology, 9:41. 2009.
[35]  Gass, J., Bethune, M.T., Siegel, M., Spencer, A., Khosla, C. Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue. Gastroenterology, 133 (2):472-80. 2007.
[36]  Senger, S., Luongo, D., Maurano, F., Mazzeo, M.F., Siciliano, R.A., Gianfrani, C., David, C., Troncone, R., Auricchio, S., Rossi, M. Intranasal administration of a recombinant alpha-gliadin down-regulates the immune response to wheat gliadin in DQ8 transgenic mice. Immunology letters, 88 (2):127-34. 2003.
[37]  Aziz, I., Evans, K.E., Papageorgiou, V., Sanders, D.S. Are patients with coeliac disease seeking alternative therapies to a gluten-free diet? Journal of gastrointestinal and liver diseases: JGLD, 20 (1):27-31. 2011.
[38]  Maiuri, L., Ciacci, C., Ricciardelli, I., Vacca, L., Raia, V., Rispo, A., Griffin, M., Issekutz, T., Quaratino, S., Londei, M. Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology, 129 (5):1400-13. 2005.
[39]  Xia, J., Bergseng, E., Fleckenstein, B., Siegel, M., Kim, C.Y., Khosla, C., Sollid, L.M. Cyclic and dimeric gluten peptide analogues inhibiting DQ2-mediated antigen presentation in celiac disease. Bioorganic & medicinal chemistry, 15 (20):6565-73. 2007.
[40]  Rivera-Nieves, J., Ho, J., Bamias, G., Ivashkina, N., Ley, K., Oppermann, M., Cominelli, F. Antibody blockade of CCL25/CCR9 ameliorates early but not late chronic murine ileitis. Gastroenterology, 131 (5):1518-29. 2006.
[41]  Booth, V., Keizer, D.W., Kamphuis, M.B., Clark-Lewis, I., Sykes, B.D. The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry, 41 (33):10418-25. 2002.
[42]  Gillett, H.R., Arnott, I.D., McIntyre, M., Campbell, S., Dahele, A., Priest, M., Jackson, R., Ghosh, S. Successful infliximab treatment for steroid-refractory celiac disease: a case report. Gastroenterology, 122 (3):800-5. 2002.
[43]  Bethune, M.T., Siegel, M., Howles-Banerji, S., Khosla, C. Interferon-gamma released by gluten-stimulated celiac disease-specific intestinal T cells enhances the transepithelial flux of gluten peptides. The Journal of pharmacology and experimental therapeutics, 329 (2):657-68. 2009.
[44]  Anderson, R.P., van Heel, D.A., Tye-Din, J.A., Jewell, D.P., Hill, A.V. Antagonists and non-toxic variants of the dominant wheat gliadin T cell epitope in coeliac disease. Gut, 55 (4):485-91. 2006.
[45]  Paterson, B.M., Lammers, K.M., Arrieta, M.C., Fasano, A., Meddings, J.B. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Alimentary pharmacology & therapeutics, 26 (5):757-66. 2007.
[46]  Malamut, G., El Machhour, R., Montcuquet, N., Martin-Lanneree, S., Dusanter-Fourt, I., Verkarre, V., Mention, J.J., Rahmi, G., Kiyono, H., Butz, E.A., Brousse, N., Cellier, C., Cerf-Bensussan, N., Meresse, B. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. The Journal of clinical investigation, 120 (6):2131-43. 2010.
[47]  Goldberg, R.F., Austen, W.G., Jr., Zhang, X., Munene, G., Mostafa, G., Biswas, S., McCormack, M., Eberlin, K.R., Nguyen, J.T., Tatlidede, H.S., Warren, H.S., Narisawa, S., Millan, J.L., Hodin, R.A. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proceedings of the National Academy of Sciences of the United States of America, 105 (9):3551-6. 2008.
[48]  Molnar, K., Vannay, A., Sziksz, E., Banki, N.F., Gyorffy, H., Arato, A., Dezsofi, A., Veres, G. Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease. Virchows Archiv: an international journal of pathology, 460 (2):157-61. 2012.
[49]  Rentea, R.M., Liedel, J.L., Fredrich, K., Welak, S.R., Pritchard, K.A., Jr., Oldham, K.T., Simpson, P.M., Gourlay, D.M. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model. The Journal of surgical research, 177 (2):228-34. 2012.