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A gluten-free diet (GFD) is currently the only treatment available for patients with celiac disease (CD). However, adherence to a GFD can be challenging because gluten is present in many foods. A lifelong follow-up of patients with CD must be performed to promote adherence to a GFD and to identify the appearance of symptoms and the associated diseases. Therefore, the development of tools to analyze gluten exposure in these patients is important. This study proposes the development of the first automatable ELISA to monitor adherence to a GFD through the quantification of urine gluten immunogenic peptides (u-GIP). Seven healthy volunteers without suspicion of CD and 23 patients with CD were monitored as part of this study to optimize, validate, and apply this assay. Non-interference was found in the urine matrix, and the recovery percentage for spiked samples was 81–101%. The u-GIP was stable for up to 16 days when the samples were stored at different temperatures. Overall, 100% of the patients had detectable u-GIP at diagnosis (range of 0.39–2.14 ng GIP/mL), which reduced to 27% after 12 months on a GFD. Therefore, this highly sensitive immunoassay would allow the analysis of u-GIP from a large battery of samples in clinical laboratories of specialized healthcare centers.

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 G