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
ARTICLE HIGHLIGHTS
Research background

A lifelong strict gluten-free diet (GFD) is the only available treatment for celiac disease (CeD), which reduces symptoms and allows the healing of the intestinal mucosa, preventing long-term complications. However, total exclusion of gluten is difficult to achieve in practice and voluntary and involuntary transgressions are highly frequent.

Research motivation

Gluten immunogenic peptides (GIP) detection in stool and urine is becoming increasingly apparent as a noninvasive and reliable marker for close and efficient GFD monitoring in patients with CeD.

Research objectives

The authors aimed to summarize published data regarding the performance of GIP determination in stool and urine in comparison to other available tools in assessing GFD adherence in patients with CeD.

Research methods

The authors conducted a systematic review searching in PubMed and Web of Science clinical studies that reported the performance of GIP determination in stool and/or urine with other biomarkers for the evaluation of treatment adherence in adult and pediatric patients with CeD.

Research results

The authors screened 67 articles and 15 articles were included for full-text analysis. In the selected publications GIP determination in stool and/or urine were compared with at least one of the following markers: levels of CeD-specific serology, results from CeD-specific non-specific questionnaires, symptomatology, and duodenal biopsy. Fecal determination by ELISA was the most investigated GIP marker, followed by urine rapid test and stool rapid test. Variability was seen in the concordance between the different tools among the studies reviewed due to the differences found in the study design, the target population, and the methods used. One of the main outcome measures reviewed was the diagnostic accuracy of these tools in assessing mucosal healing. An association of mucosal status and GIP detection was observed in some publications, where serology, questionnaires, and symptomatology showed lower sensitivity. Furthermore, GIP detection may help in symptomatic patients to determine whether non-responsive CeD or refractory CeD occurs due to recurrent gluten exposure or due to additional factors.

Research conclusions

The introduction of GIP detection in stool and/or urine as a non-invasive marker for GFD monitoring in patients with CeD may reduce health expenditure by preventing future complications arising from gluten exposure not detectable by other tools in use. Stool and urine rapid tests may be an option for disease self-managing by the patient, while fecal ELISA test could be used for GIP quantification in the laboratory.

Research perspectives

The introduction of algorithms for GIP determination within the follow-up of patients with CeD in guidelines will allow its routine use in clinical practice. In addition, future studies may also determine their utility for other applications such as the confirmation of gluten consumption during the diagnosis process or the investigation of gluten metabolism.