Gluten peptides in urine correlate with mucosal damage in celiac disease

Researchers developed a novel test that detects gluten immunogenic peptides in urine, the levels of which were found to correlate with mucosal damage in patients with celiac disease, according to data presented at UEG Week 2015.

“There is no test to measure gluten consumption in the U.S., and it is really hard for patients to avoid gluten; this leads to contamination and complications in celiac disease,” Francisco León, MD, PhD, CEO and chief medical officer of Celimmune and adjunct professor of medicine at Jefferson Medical College in Philadelphia, told Healio Gastroenterology. This “is the second method developed to measure gluten in Europe, after the gluten stool test ELISA developed by the same diagnostics company in Spain (Biomedal). This urine test is a lateral flow test with a couple of very sensitive antibodies discovered by Biomedal (G12 and A1) which recognize gluten immunogenic peptides (GIPs) after they have gone through the circulation and are excreted in the urine.”

Francisco León

In a clinical trial, León and colleagues collected urine samples from 76 healthy individuals and 58 patients with celiac disease, and tested the samples for gluten immunogenic peptides using this method. Samples were collected at different time points during which participants were subjected to different dietary conditions.

“The results were quite striking,” León said. “About half of the celiac patients on a gluten-free diet studied had detectable amounts of gluten in their urine. Secondly, there was a very good correlation between the presence of these levels of urinary gluten and mucosal damage.”

Gluten immunogenic peptides were detected in concentrated urine samples from healthy individuals as early as 4 to 6 hours after consuming gluten, and remained detectable for 1 to 2 days after a one-time consumption of gluten following a gluten-free diet washout period. The gluten immunogenic peptides were detected with high sensitivity at levels as low as 50 mg gluten. The test appeared to show nonadherence to gluten-free diet or gluten contamination in the patients with celiac disease, given the aforementioned detectable gluten immunogenic peptides in the urine of celiac patients.

Furthermore, urinary gluten and mucosal damage in celiac patients was found to correlate; a retrospective analysis of duodenal biopsies in 27 celiac patients showed 90% with no villus atrophy did not have detectable gluten immunogenic peptides in their urine.

“Most patients found to have gluten in their urine [met] Marsh 2 or Marsh 3 [criteria], which is a histological definition of mucosal damage,” León said. “Another interesting clinical aspect of measuring gluten in bodily fluids, in this case in studies done in feces, is that the positivity increases with age, suggesting that children are well controlled, but as patients become teenagers and [move] into adult life, they’re less able to control their diet. Interestingly, in these studies, boys were much less compliant than girls in following the gluten-free diet.

“We are excited about this test because [once approved, celiac] patients will potentially be able … to control their intake of food, better manage their diet and more precisely identify contamination with gluten, hopefully improving their ability to avoid it,” León said.

The researchers concluded that the test will also be useful in therapeutic research of novel non-dietary approaches to celiac disease, which will come handy for over a dozen start-ups developing therapies for celiac disease at this time. – by Adam Leitenberger

Reference:

de Lourdes Moreno Amador M, et al. Abstract OP013. Presented at: UEG Week; Oct. 24-27, 2015; Barcelona, Spain.

Disclosures: Francisco Leon reports he is a stockholder in Biomedal and Celimmune.