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  • 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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Coeliac disease
Original article
Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing
  1. María de Lourdes Moreno1,
  2. Ángel Cebolla2,
  3. Alba Muñoz-Suano2,
  4. Carolina Carrillo-Carrion2,
  5. Isabel Comino1,
  6. Ángeles Pizarro3,
  7. Francisco León4,
  8. Alfonso Rodríguez-Herrera5,
  9. Carolina Sousa1
  1. 1Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain
  2. 2Biomedal S.L., Sevilla, Spain
  3. 3Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain
  4. 4Celimmune, Bethesda, Maryland, USA
  5. 5Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain
  1. Correspondence to Professor Carolina Sousa, Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, C/ Profesor García González 2, Sevilla 41012, Spain; csoumar{at}us.es

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.

  • CELIAC DISEASE
  • GLUTEN FREE DIET

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/gutjnl-2015-310148

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    Footnotes

    • Contributors Study concept and design: MLM, ÁC and CS; acquisition of data: MLM, CC-C and AM-S; data analysis and interpretation: MLM, ÁC, AM-S, ÁP, FL, AR-H and CS; technical and material support: MLM, CC-C, IC, AM-S, ÁP and AR-H; manuscript drafting: MLM, ÁC, FL and CS; critical revision of the manuscript: ÁC, FL and CS.

    • Funding This work was supported by grants from Ministerio de Ciencia e Innovación and FEDER funds (DELIAC, IPT-2011-0952-900000), Asociación de Celíacos de Madrid y Sensibles al Gluten and Corporación Tecnológica de Andalucía (SINGLUCHECK, 1737/0118).

    • Competing interests ÁC and FL own stock in Biomedal SL. Other authors have declared no conflict of interest. The method of this manuscript was included in a patent application by MLM, CS, AR-H and ÁC as inventors with the assigned number P201400569.

    • Patient consent Obtained.

    • Ethics approval The local Ethics Committee of the Hospital Virgen de Valme (Sevilla, Spain).

    • Provenance and peer review Not commissioned; externally peer reviewed.