Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces
Isabel Comino, Ana Real, Santiago Vivas, Miguel Ángel Síglez, Alberto Caminero, Esther Nistal, Javier Casqueiro, Alfonso Rodríguez-Herrera, Angel Cebolla, Carolina Sousa, Isabel Comino, Ana Real, Santiago Vivas, Miguel Ángel Síglez, Alberto Caminero, Esther Nistal, Javier Casqueiro, Alfonso Rodríguez-Herrera, Angel Cebolla, Carolina Sousa
Abstract
Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available.
Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces.
Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody.
Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients.
Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867.
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References
- Fasano A. Surprises from celiac disease. Sci Am 2009;301:54–61
- Ganapathy V, Gupta N, Martindale RG. Physiology of the gastrointestinal tract. 4th ed. New York, NY: Johnson LR, 2006
- Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C. Structural basis for gluten intolerance in celiac sprue. Science 2002;297:2275–9
- Bethune MT, Crespo-Bosque M, Bergseng E, Mazumdar K, Doyle L, Sestak K, Sollid LM, Khosla C. Noninflammatory gluten peptide analogs as biomarkers for celiac sprue. Chem Biol 2009;16:868–81
- Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, Henderson K, Mannering SI, Gianfrani C, Jewell DP, et al. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med 2010;2:41ra51
- Silvester JA, Rashid M. Long-term follow-up of individuals with celiac disease: an evaluation of current practice guidelines. Can J Gastroenterol 2007;21:557–64
- Hadithi M, Peña AS. Current methods to diagnose the unresponsive and complicated forms of coeliac disease. Eur J Intern Med 2010;21:247–53
- Walker MM, Murray JA. An update in the diagnosis of disease. Histopathology 2011;59:166–79
- Fernández-Calle P, Codoceo R, Polanco I, Gómez-Cerezo J, Orsi M, Tenias JM. Is an intestinal permeability test a valid marker for slight dietary transgressions in adolescents with coeliac disease? Gut 1993;34:774–7
- Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol 2010;7:204–13
- Selimoğlu MA, Karabiber H. Celiac disease: prevention and treatment. J Clin Gastroenterol 2010;44:4–8
- Duerksen DR, Wilhelm-Boyles C, Parry DM. Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet. Dig Dis Sci 2005;50:785–90
- Ertekin V, Selimoğlu MD, Turgut A, Bakan N. Fecal calprotectin concentration in celiac disease. J Clin Gastroenterol 2010;44:544–6
- Morón B, Cebolla A, Manyani H, Alvarez-Maqueda M, Megías M, Thomas M C, López MC, Sousa C. Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide. Am J Clin Nutr 2008;87:405–14
- Morón B, Bethune M, Comino I, Manyani H, Ferragud M, López MC, Cebolla A, Khosla C, Sousa C. Toward the assessment of food toxicity for celiac patients: Characterization of monoclonal antibodies to a main immunogenic gluten peptide. PLoS ONE 2008;3:e2294.
- Marsh MN, Crowe PT. Morphology of the mucosal lesion in gluten sensitivity. Baillieres Clin Gastroenterol 1995;9:273–93
- Comino I, Real A, de Lorenzo L, Cornell H, López-Casado MÁ, Barro F, Lorite P, Torres MI, Cebolla A, Sousa C. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in celiac disease. Gut 2011;60:915–22
- Sousa C, Johansson C, Charon C, Manyani H, Sautter C, Kondorosi A, Crespi M. Translational and structural requirements of the early nodulin gene enod40, a short-open reading frame-containing RNA, for elicitation of a cell-specific growth response in the alfalfa root cortex. Mol Cell Biol 2001;21:354–66
- Catassi C, Fabiani E, Iacono G, D'Agate C, Francavilla R, Biagi F, Volta U, Accomando S, Picarelli A, De Vitis I, et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007;85:160–6
- Sonnenburg JL, Fischbach MA. Community health care: therapeutic opportunities in the human microbiome. Sci Transl Med 2011;3:78ps12
- Ehren J, Morón B, Martin E, Bethune MT, Gray GM, Khosla C. A food-grade enzyme preparation with modest gluten detoxification properties. PLoS ONE 2009;4:e6313.
- Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol 2007;5:445–50
- Shan L, Qiao SW, Arentz-Hansen H, Molberg Ø, Gray GM, Sollid LM, Khosla C. Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue. J Proteome Res 2005;4:1732–41
Source: PubMed