Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients
Ana Florencia Costa, Emilia Sugai, María de la Paz Temprano, Sonia Isabel Niveloni, Horacio Vázquez, María Laura Moreno, M. Remedios Domínguez-Flores, Alba Muñoz-Suano, Edgardo Smecuol, Juan Pablo Stefanolo, Andrea F González, Angel Cebolla-Ramirez, Eduardo Mauriño, Elena F Verdú, Julio César Bai
Ana Florencia Costa, Emilia Sugai, María de la Paz Temprano, Sonia Isabel Niveloni, Horacio Vázquez, María Laura Moreno, Edgardo Smecuol, Juan Pablo Stefanolo, Andrea F González, Eduardo Mauriño, Julio César Bai: Small Bowel Section, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1263, Argentina
M. Remedios Domínguez-Flores, Alba Muñoz-Suano, Angel Cebolla-Ramirez, Department of Immunology, Biomedal S.L., Sevilla 41092, Spain
Elena F Verdú, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S4L8, Canada
Julio César Bai, Research Institutes, Universidad del Salvador, Buenos Aires 1050, Argentina
Author contributions: Costa AF contributed with patient enrolment and analysis of data; Sugai E performed biochemical tests, data analysis and interpretation; Temprano MdlP contributed to patient enrolment, dietary reports and assessment of compliance; Niveloni SI contributed to study design and patient enrolment; Vázquez H contributed to statistical analysis and data interpretation; Moreno ML contributed to patient enrolment and data analysis. Domínguez-Flores MR contributed with reagents; Muñoz-Suano A contributed with reagents; Smecuol E contributed to the study design and patient enrolment; Stefanolo JP contributed to data analysis; Gónzalez A contributed to dietary reports and assessment of compliance; Cebolla-Ramirez A contributed to study design and development of GIP tests; Mauriño E contributed to study design and critical review of the manuscript; Verdú EF contributed to language editing and critical revision of the manuscript for intellectual content; Bai JC contributed to study concept and design, analysis and interpretation of data, study direction and manuscript writing; All authors read and approved the final manuscript.
Institutional review board statement: The study was approved by Local Institutional Review Committees for Research and Ethics.
Informed consent statement: All patients signed a written informed consent approved by the Local Ethics Committee.
Conflict-of-interest statement: Authors from Biomedal S.L. did not participate in the study design, data analysis and writing of the manuscript. The remaining authors have no conflicts to disclose.
STROBE statement: The authors have read and checked the STROBE checklist.
Open-Access: This 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 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/
Corresponding author: Julio César Bai, MD, Professor Emeritus, Small Bowel Section, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Av. Caseros 2061, Buenos Aires 1264, Argentina. jbai@intramed.net
Telephone: +54-11-43041018 Fax: +54-11-43041018
Received: December 14, 2018
Peer-review started: December 14, 2018
First decision: December 28, 2018
Revised: January 8, 2018
Accepted: January 14, 2019
Article in press: January 14, 2019
Published online: March 21, 2019
ARTICLE HIGHLIGHTS
Research background
Until now, there was no objective test to reveal objectively ingested gluten in clinical practice. Recently developed stool and urine laboratory tests based on monoclonal antibody technology specifically determine consumption of gluten by assessing the excretion of gluten immunogenic peptides (GIP). These tests were proposed to help in the monitoring of adherence to the gluten-free diet (GFD). More recently, point-of-care tests (PoCT) for stool and urine have been developed that may encourage patient self-monitoring and better compliance with disease management.
Research motivation
Despite recent research, there are at least three unsolved issues regarding the use of objective tests to detect gluten consumption. (1) The utility of GIP excretion tests, in patients with CeD who consider themselves adherent to the GFD, has not been compared with conventional monitoring methods in a real-life-scenario; (2) It is unknown whether consumption of gluten as measured by GIP excretion is different in symptomatic and asymptomatic CeD patients while on GFD; and (3) It is unclear how the new PoCT tests compare with laboratory-performed GIP tests.
Research objectives
We assessed (1) the performance of enzyme-linked immunosorbent assays (ELISA) and point-of-care (PoCTs) GIP excretion tests in patients with CeD on GFD; and (2) its relation to the presence of symptoms.
Research methods
We conducted an observational, prospective, cross-sectional study in CeD patients on a GFD for at least two years. Patients were categorized as asymptomatic or symptomatic at enrollment, using the Gastrointestinal Symptom Rating Scale questionnaire. Gluten consumption was assessed by 3-d dietary recall and GIP excretion in stool by ELISA, and by PoCTs in stool and urine using commercial kits.
Research results
Forty-four of the sixty-two screened CeD patients were enrolled; nineteen (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. At least one positive GIP test was detected in 11 out of the total 44 (25.0%) patients,32% of whom were asymptomatic. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT tests detected dietary indiscretions. Excretion of GIP was detected in 7(8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports.
Research conclusions
Our study shows that GIP determination in stool and urine detects dietary transgressions in patients on long-term GFD who are unaware of gluten consumption. Our data also suggest that PoCT for GIP detection in stool and urine constitutes simple home-based methods that may aid in self-assessment of dietary indiscretions, especially inadvertent contaminations.GIP excretion is evident in treated patients, irrespective of the presence of symptoms. This observation confirms that patients should be assessed even when they are asymptomatic and/or have negative serology.
Research perspectives
The results support the use of specific GIP tests in stool and urine in conjunction with conventional strategies used to determine adherence to the GFD. One potential future research direction includes the use of these new tools to determine patterns of adherence in patients who believe to be adherent to the GFD. PoCT tests might encourage patients to be involved in self-monitoring and, thus, improve adherence to the diet.
