Measuring Excretion of Gluten Immunogenic Peptides (GIPs): An Assay for Monitoring Gluten Exposure

Abstract

Individuals with coeliac disease are required to exclude all gluten from their diet to prevent small bowel inflammation and associated complications. Life-long adherence to a gluten-free diet is challenging because of the potential presence of gluten in common noncereal foods, cross-contamination, and potentially small amounts of gluten in cereal-based foods formally labelled as “gluten-free.” For people living with coeliac disease, current tests to monitor the efficacy of a gluten-free diet may not detect ongoing, low level, or intermittent unintentional gluten exposure. The iVYCHECK and iVYLISA assays by Biomedal detect gluten-derived peptides, which are resistant to digestion, known to be immunogenic and are excreted in urine and stool. The urine test is qualitative for recent short-term exposure while the faecal test is quantitative and reflects gluten exposure over a longer interval. Several studies have validated the performance of these assays in monitoring compliance to gluten-free diets. We sought to evaluate these assays in a community-based pathology service by comparing values obtained in individuals with no dietary restrictions compared with those following a gluten-free diet. We performed 124 assays in 21 subjects over 9 days. The quantitative faecal gluten immunogenic peptide assay was highly precise. Faecal gluten immunogenic peptide assays were moderately sensitive (66%) and highly specific (97%) while the urine assay had sensitivity of 100% and lesser specificity (48%). Both assays had very high negative predictive value (90%) for detection of clinically relevant levels of oral gluten, as verified by participant self-reported diet diary over a 9-day period. An episode of inadvertent gluten exposure in one individual on an otherwise gluten-free diet was associated with temporally high gluten immunogenic peptide levels in stool. The majority of participants regarded accidental gluten exposures as important to their health and rated monitoring for gluten contamination as their strongest reason for utilizing this assay. Our study was limited by use of self-report rather than independent tests of gluten intake or clinical disease markers; however, our findings do provide support for implementation of these assays to assist in monitoring efficacy of a gluten-free diet.