Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing
Open accessAbstract
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 measuredNegative TGA results do not correlate well with dietary compliance.
“negative TGA results do not correlate well with dietary compliance (21, 54).”
From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [54]
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ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.
Mearin, M. L., Agardh, D., Antunes, H., Al‐toma, A., Auricchio, R., Castillejo, G., Catassi, C., Ciacci, C., Discepolo, V., Dolinsek, J., et al. (2022) · Journal of pediatric gastroenterology and nutrition · doi:10.1097/mpg.0000000000003540 · Cited by 186 · see citing works
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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
- PMC
- PMC5284479
- 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
- hybrid
- doi.org
- 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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