Determination of Urinary Gluten Immunogenic Peptides to Assess Adherence to the Gluten-Free Diet: A Randomized, Double-Blind, Controlled Study

Abstract

INTRODUCTION: The adherence to a gluten-free diet (GFD) is a trending topic in the management of celiac disease. The aim of our study was to evaluate the diagnostic performance of urinary gluten immunogenic peptides (GIP) determination to detect gluten contamination of the GFD. METHODS: In study A, 25 healthy adults on a standard GFD performed 6 gluten challenges (0, 10, 50, 100, 500, and 1,000 mg) with quantification of urinary GIP before (T 0 ) and during the following 24 hours. In study B, 12 participants on a gluten contamination elimination diet underwent urinary GIP determination at T 0 and after challenge with 5 or 10 mg gluten. Urine GIP concentration was determined by an immunochromatographic assay. RESULTS: In study A, 51 of 150 baseline urine samples were GIP+ on GFD and 7 of 17 were GIP+ after the zero-gluten challenge, whereas only 55 of 81 were GIP+ after the 10–1,000 mg gluten challenges. There was no significant change in the 24-hour urinary GIP when increasing gluten from 10 to 1,000 mg. In study B, 24 of 24 baseline urine samples were GIP−, whereas 8 of 24 were GIP+ after 5 or 10 mg of gluten. DISCUSSION: Traces of gluten in the standard GFD may cause positivity of urinary GIP determination, whereas a false negativity is common after a gluten intake of 10–1,000 mg. Owing to the impossibility of standardizing the test in normal conditions, it seems unlikely that urinary GIP determination may represent a reliable tool to assess the compliance to the GFD of patients with celiac disease or other gluten-related disorders.

Controls and Result Interpretations in Studies of Urine Gluten Peptide Determinations

“…In conclusion, the suggestions of Monachesi et al (1) of false positive and negative results in their study were likely misinterpreted, and we encourage the authors to conduct the appropriate controls.…”

Review article: therapeutic targets for the pharmacologic management of coeliac disease—the future beyond a gluten‐free diet

“…Other methods of verifying gluten avoidance based on serology, urine or stool tests are being evaluated but have not yet received regulatory approval. For example, immunochromatographic tests that determine excretion of gluten immunogenic peptides (GIP) in urine and stool may serve as markers of persistent dietary gluten, although the reliability of these tests for accurately quantifying exposure is unclear 52–54 …”

“…For example, immunochromatographic tests that determine excretion of gluten immunogenic peptides (GIP) in urine and stool may serve as markers of persistent dietary gluten, although the reliability of these tests for accurately quantifying exposure is unclear. [52][53][54] Finally, patients with confirmed RCD (as opposed to patients with non-responsive CeD) represent a unique phenotype that requires special consideration. There are two types of RCD (RCD-I and RCD-II), based on the presence of aberrant IELs, characterised by deficiencies in surface CD3 with retained intracellular CD3, and clonal rearrangement of the T-cell receptor (TCR).…”

Nutrition in Patients with Lactose Malabsorption, Celiac Disease, and Related Disorders

“…Testing GIP in both urine and stool samples has been reported to detect gluten consumption in celiac patients and was concordant with over 65% of dietary reports. Testing was performed by enzyme-linked immunosorbent assay (ELISA) for stool and point-of-care tests (POCTs) for GIP excretion in urine and stool [ 149 ]; however, the lack of standardization in urinary GIP makes it an unreliable tool to assess adherence to the GFD [ 150 ]. Measuring GIP in stool of celiac patients may be helpful for monitoring GFD compliance [ 151 , 152 ].…”