Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2021; 27(37): 6306-6321
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6306
Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review
Laura Coto, Irati Mendia, Carolina Sousa, Julio César Bai, Angel Cebolla
Laura Coto, Irati Mendia, Angel Cebolla, Research and Development, Biomedal, Camas 41900, Seville, Spain
Laura Coto, Human Nutrition and Food Science Doctoral Program, University of Granada, Granada 18011, Spain
Irati Mendia, Molecular Biology, Biomedicine and Clinical Research Doctoral Program, University of Seville, Seville 41012, Spain
Carolina Sousa, Department of Microbiology and Parasitology, University of Seville, Seville 41013, Spain
Julio César Bai, Department of Gastroenterology, Dr. Carlos Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina
Julio César Bai, Research Institutes, Universidad del Salvador, Buenos Aires 1050, Argentina
Author contributions: Coto L, Mendia I, Sousa C, Bai JC and Cebolla A contributed equally to the revision of the literature, wrote the draft, and/or revised the final manuscript for intellectual content.
Supported by Ministerio de Ciencia e Innovación, No. DI-16-08943 and No. DI-17-09627.
Conflict-of-interest statement: Angel Cebolla is the founder and current CEO of Biomedal S.L., Angel Cebolla and Carolina Sousa are inventors of the patent "Detecting gluten peptides in human fluids" (No. WO/2016/005643), Laura Coto and Irati Mendia are employees at Biomedal S.L., Julio César Bai declares no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution-NonCommercial (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/
Corresponding author: Julio César Bai, MD, Professor, Department of Gastroenterology, Dr. Carlos Bonorino Udaondo Gastroenterology Hospital, Av. Caseros 2061, Buenos Aires 1264, Argentina. jbai@intramed.net
Received: March 22, 2021
Peer-review started: March 22, 2021
First decision: June 14, 2021
Revised: June 28, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 7, 2021
Processing time: 191 Days and 0.3 Hours
Abstract
BACKGROUND

Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease (CeD). Gluten immunogenic peptides (GIP) are resistant to gastrointestinal digestion and are then excreted via the stool and urine. Most common detection methods applied in the follow-up visits for CeD patients such as serology tests, dietetic interviews, questionnaires, and duodenal biopsy have been proved to be inefficient, invasive, or inaccurate for evaluating gluten-free diet (GFD) compliance. Determination of excreted GIP in stool and urine has been developed as a non-invasive, direct, and specific test for GFD monitoring.

AIM

To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring.

METHODS

PubMed and Web of Science searches were performed using the keywords “gluten immunogenic peptides” or “gluten immunogenic peptide” and a combination of the previous terms with “feces”, “stools”, “urine”, “celiac disease”, “gluten-free diet”, and “adherence” to identify relevant clinical studies published in English and Spanish between 2012 to January 2021. Reference lists from the articles were reviewed to identify additional pertinent articles. Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included. Case reports, commentaries, reviews, conference papers, letters, and publications that did not focus on the aims of this review were excluded.

RESULTS

Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools. Studies included both children and adults diagnosed with CeD and healthy volunteers. Overall, these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD. Tools identified in this work included the CeD-specific serology, dietetic questionnaires, symptomatology, and the duodenal biopsy. Review of the literature revealed that the rates of GFD adherence may vary between 30%-93% using either stool or urine GIP determination, 49%-96% by the serology, 59%-94% using the dietetic questionnaires, 56%-95% by the reported symptoms and 44%-76% with the duodenal biopsy. In addition, the association between the different methods and histological abnormalities (Marsh II-III) was found to be 33%-100% for GIP determination (stool and urine), 25%-39% for CeD-specific serology, 3%-50% for dietetic questionnaires, and 22%-28% for the symptomatology.

CONCLUSION

Excreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure.

Keywords: Celiac disease; Gluten-free diet; Gluten immunogenic peptides; Immunoassays; Stool; Urine

Core Tip: A strict gluten-free diet (GFD) is the only available treatment for celiac disease. However, treatment adherence is difficult due to the ubiquitous nature of gluten, hurting patients’ quality of life. Despite several tests to evaluate GFD compliance, it has been proven to be invasive or inefficient. The determination of gluten immunogenic peptides (GIP) in stool and urine has been developed as a non-invasive, direct, and specific test for GFD monitoring. We herein summarized the current available literature meeting the clinical utility of GIP determination compared to the available tools in use.