Cited by 317Celiac Disease Research and ManagementWheat and Barley Genetics and PathologyInflammatory Bowel Disease

Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing

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Moreno, María de Lourdes, Cebolla, Ángel, Muñoz-Suano, Alba, Carrillo-Carrion, Carolina, Comino, Isabel, Pizarro, Ángeles, León, Francisco, Rodríguez-Herrera, Alfonso +1 more·2017·Gut

Abstract

Objective: Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage. Design: Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines. Results: GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4–6 h after single gluten intake, and remained detectable for 1–2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery. Conclusion: GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development. Trial registration number: NCT02344758.

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  • Repeated GIP positivity over a span of multiple days correlates with intestinal mucosa damage.

    “Repeated GIP positivity over a span of multiple days has been reported to correlate with intestinal mucosa damage (49, 54).”

    From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [54]

    The Results section, “Dietary transgressions in adult patients with CD: correlation with mucosal damage” (page unavailable), reports a significant correlation between urinary GIP and severity of intestinal mucosal damage in 25 adults with coeliac disease. It does not establish that positivity repeated over multiple days correlates with damage; the multi-day urine monitoring described elsewhere in Results involved healthy volunteers. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Negative TGA results do not correlate well with dietary compliance.

    “negative TGA results do not correlate well with dietary compliance (21, 54).”

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Research works printed but not linked: 43

  1. [1]Bernardo D, Peña AS Developing strategies to improve the quality of life of patients with gluten intolerance in patients with and without coeliac disease. Eur J Intern Med 2012; 23: 6– 8. 10.1016/j.ejim.2011.09.016 22153523 · DOI
  2. [2]Hall NJ, Rubin GP, Charnock A Intentional and inadvertent non-adherence in adult coeliac disease. A cross-sectional survey. Appetite 2013; 68: 56– 62. 10.1016/j.appet.2013.04.016 23623778 · DOI
  3. [3]Freeman HJ Non-dietary forms of treatment for adult celiac disease. World J Gastrointest Pharmacol Ther 2013; 4: 108– 12. 10.4292/wjgpt.v4.i4.108 24199026 PMC3817285 · DOI
  4. [4]Barratt SM, Leeds JS, Sanders DS Quality of life in coeliac disease is determined by perceived degree of difficulty adhering to a gluten-free diet, not the level of dietary adherence ultimately achieved. J Gastrointest Liver Dis 2011; 20: 241– 5. 21961090
  5. [5]Matoori S, Fuhrmann G, Leroux JC Celiac disease: a challenging disease for pharmaceutical scientists. Pharm Res 2013; 30: 619– 26. 10.1007/s11095-012-0951-x 23229860 · DOI
  6. [6]Tio M, Cox MR, Eslick GD Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther 2012; 35: 540– 51. 10.1111/j.1365-2036.2011.04972.x 22239821 · DOI
  7. [7]Stoven S, Murray JA, Marietta E Celiac disease: advances in treatment via gluten modification. Clin Gastroenterol Hepatol 2012; 10: 859– 62. 10.1016/j.cgh.2012.06.005 22728383 PMC3788609 · DOI
  8. [8]Bai J, Zeballos E, Fried M, et al WGOOMGE practice guideline coeliac disease. World Gastroenterol News 2012; 2: S1– 8.
  9. [9]Dipper CR, Maitra S, Thomas R, et al Anti-tissue transglutaminase antibodies in the follow-up of adult coeliac disease. Aliment Pharmacol Ther 2009; 30: 236– 44. 10.1111/j.1365-2036.2009.04039.x 19438848 · DOI
  10. [10]Vives-Pi M, Takasawa S, Pujol-Autonell I, et al Biomarkers for diagnosis and monitoring of celiac disease. J Clin Gastroenterol 2013; 47: 308– 13. 10.1097/MCG.0b013e31827874e3 23388848 · DOI
  11. [11]Vallejo-Diez S, Bernardo D, Moreno ML, et al Detection of specific IgA antibodies against a novel deamidated 8-Mer gliadin peptide in blood plasma samples from celiac patients. PLoS ONE 2013; 8: e80982 10.1371/journal.pone.0080982 24278359 PMC3838339 · DOI
  12. [12]Sharkey LM, Corbett G, Currie E, et al Optimising delivery of care in coeliac disease - comparison of the benefits of repeat biopsy and serological follow-up. Aliment Pharmacol Ther 2013; 38: 1278– 91. 10.1111/apt.12510 24117503 · DOI
  13. [13]Tursi A, Brandimarte G, Giorgetti GM Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease. J Clin Gastroenterol 2003; 37: 387– 91. 10.1097/00004836-200311000-00007 14564185 · DOI
  14. [14]Rashtak S, Ettore MW, Homburger HA, et al Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol 2008; 6: 426– 32. 10.1016/j.cgh.2007.12.030 18304884 PMC2440671 · DOI
  15. [15]Kaukinen K, Sulkanen S, Mäki M, et al IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in coeliac disease. Eur J Gastroenterol Hepatol 2002; 14: 311– 15. 10.1097/00042737-200203000-00017 11953698 · DOI
  16. [16]Kaukinen K, Peräaho M, Lindfors K, et al Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237– 45. 10.1111/j.1365-2036.2007.03311.x 17451570 · DOI
  17. [17]Tursi A, Brandimarte G, Giorgetti GM, et al Endoscopic and histological findings in the duodenum of adults with celiac disease before and after changing to a gluten-free diet: a 2-year prospective study. Endoscopy 2006; 38: 702– 7. 10.1055/s-2006-925178 16810593 · DOI
  18. [18]Comino I, Real A, Vivas S, et al Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr 2012; 95: 670– 7. 10.3945/ajcn.111.026708 22258271 PMC3278243 · DOI
  19. [19]Esteban M, Castaño A Non-invasive matrices in human biomonitoring: a review. Environ Int 2009; 35: 438– 49. 10.1016/j.envint.2008.09.003 18951632 · DOI
  20. [20]Pinches M, Betts C, Bickerton S, et al Evaluation of novel renal biomarkers with a cisplatin model of kidney injury: gender and dosage differences. Toxicol Pathol 2012; 40: 522– 33. 10.1177/0192623311432438 22491933 · DOI
  21. [21]Li PKT, Burdmann EA, Mehta RL Acute kidney injury: global health alert. Transplantation 2013; 5: 653– 7. 23503499
  22. [22]Marsh MN Gluten, major histocompatibility complex, and the small intestine: a molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 1992; 102: 330– 54. 1727768
  23. [23]Oberhuber G, Granditsch G, Vogelsang H The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999; 11: 1185– 94. 10.1097/00042737-199910000-00019 10524652 · DOI
  24. [24]Herman ML, Rubio-Tapia A, Lahr BD, et al Patients with celiac disease are not followed up adequately. Clin Gastroenterol Hepatol 2012; 10: 893– 9. 10.1016/j.cgh.2012.05.007 22610009 PMC3402703 · DOI
  25. [25]Tack GJ, Verbeek WH, Schreurs MW, et al The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol 2010; 7: 204– 13. 10.1038/nrgastro.2010.23 20212505 · DOI
  26. [26]Walker MM, Murray JA An update in the diagnosis of coeliac disease. Histopathology 2011; 59: 166– 79. 10.1111/j.1365-2559.2010.03680.x 21054494 · DOI
  27. [27]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. 10.1007/s10620-005-2574-0 15844719 · DOI
  28. [28]Ertekin V, Selimoğlu MA, Turgut A, et al Fecal calprotectin concentration in celiac disease. J Clin Gastroenterol 2010; 44: 544– 6. 10.1097/MCG.0b013e3181cadbc0 20054281 · DOI
  29. [29]Duerksen DR, Wilhelm-Boyles C, Veitch R, et al A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet. Dig Dis Sci 2010; 55: 1026– 31. 10.1007/s10620-009-0813-5 19399613 · DOI
  30. [30]Balamtekın N, Baysoy G, Uslu N, et al Fecal calprotectin concentration is increased in children with celiac disease: relation with histopathological findings. Turk J Gastroenterol 2012; 23: 503– 8. 23161294
  31. [31]Capone P, Rispo A, Imperatore N, et al Fecal calprotectin in coeliac disease. World J Gastroenterol 2014; 20: 611– 12. 10.3748/wjg.v20.i2.611 24574734 PMC3923040 · DOI
  32. [32]Morón B, Bethune MT, Comino I, et al Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide. PLoS ONE 2008; 3: e2294 10.1371/journal.pone.0002294 18509534 PMC2386552 · DOI
  33. [33]Comino I, Real A, Moreno ML, et al Immunological determination of gliadin 33-mer equivalent peptides in beers as specific and practical analytical methods to assess safety for celiac patients. J Sci Food Agric 2013; 93: 933– 43. 10.1002/jsfa.5830 22886585 · DOI
  34. [34]Catassi C, Fabiani E, Iacono G, 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. 17209192
  35. [35]Akobeng AK, Thomas AG Systematic review: tolerable amount of gluten for people with coeliac disease. Aliment Pharmacol Ther 2008; 27: 1044– 52. 10.1111/j.1365-2036.2008.03669.x 18315587 · DOI
  36. [36]Gibert A, Kruizinga AG, Neuhold S, et al Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation. Am J Clin Nutr 2013; 97: 109– 16. 10.3945/ajcn.112.047985 23193005 · DOI
  37. [37]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. 17853949 PMC2657984
  38. [38]Woodward J The management of refractory coeliac disease. Ther Adv Chronic Dis 2013; 4: 77– 90. 10.1177/2040622312473174 23556127 PMC3610261 · DOI
  39. [39]Rubio-Tapia A, Hill ID, Kelly CP, et al ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108: 656– 76. 10.1038/ajg.2013.79 23609613 PMC3706994 · DOI
  40. [40]Arguelles-Grande C, Brar P, Green PH, et al Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease. J Clin Gastroenterol 2013; 47: 593– 601. 10.1097/MCG.0b013e31828a3c44 23470642 · DOI
  41. [41]Ilus T, Kaukinen K, Virta LJ, et al Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther 2014; 39: 418– 25. 10.1111/apt.12606 24387637 · DOI
  42. [42]Rubio-Tapia A, Murray JA Classification and management of refractory coeliac disease. Gut 2010; 59: 547– 57. 10.1136/gut.2009.195131 20332526 PMC2861306 · DOI
  43. [43]Nijeboer P, van Wanrooij RL, Tack GJ, et al Update on the diagnosis and management of refractory coeliac disease. Gastroenterol Res Pract 2013; 2013: 518483 10.1155/2013/518483 23762036 PMC3665175 · DOI

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Authors
Moreno, M. D. L., Cebolla, Á., Muñoz-Suano, A., Carrillo-Carrion, C., Comino, I., Pizarro, Á., León, F., Rodríguez-Herrera, A., & Sousa, C.
Affiliations
  • Universidad de Sevilla (ES)
  • Biomedal (Spain) (ES)
  • Biomedal S.L., Sevilla, Spain
  • Hospital Universitario Virgen del Rocío (ES)
  • Celimmune (United States) (US)
  • Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain
Corresponding author
Sousa, Carolina
Venue
Gut
Publisher
BMJ
Published
2015-11-25
Volume
66
Issue
2
Pages
250-257
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
OpenAlex
W2203036197
Cited by
317
References
0
Citations by year
2026: 8 · 2025: 22 · 2024: 41 · 2023: 32 · 2022: 40 · 2021: 51 · 2020: 43 · 2019: 23 · 2018: 29 · 2017: 17 · 2016: 10 · 2015: 1
FWCI
19.79
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Gut (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by-nc)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Ministerio de Ciencia e Innovación
  • Corporación Tecnológica de Andalucía (1737/0118)
Topics
  • Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Wheat and Barley Genetics and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
celiac disease, gluten-free diet compliance, gluten immunogenic peptides, urinary biomarkers, lateral flow tests, villous atrophy, non-invasive monitoring, gluten intake
MeSH terms
Protein Glutamine gamma Glutamyltransferase 2, Adolescent, Adult, Antibodies, Monoclonal, Biopsy, Celiac Disease, Child, Child, Preschool, Chromatography, Affinity, Duodenum, Female, Gliadin, Glutens, Humans, Immunoglobulin A, Male, Middle Aged, Patient Compliance, Peptides, Transglutaminases, Sensitivity and Specificity, Diet Records, Case-Control Studies, GTP-Binding Proteins, Diet, Gluten-Free, Young Adult

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