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Gluten challenges for people on a gluten-free diet seeking a celiac disease diagnosis may need to be increased, study suggests

May 24, 2024

Current amounts of gluten in a challenge may not lead to accurate celiac disease blood test results

By Amy Ratner, director of scientific affairs

When someone on a gluten-free diet seeks a celiac disease diagnosis, the amount of gluten in a gluten challenge may need to be increased for celiac disease test results to be accurate, suggests a study presented at Digestive Disease Week. (DDW)

Gluten is the trigger for celiac disease and someone being tested for the condition has to be consuming it in sufficient quantities in order to produce the celiac disease antibodies measured by blood tests.

The results presented by Entero Therapeutics came from a large database of celiac disease research that included findings from two Phase 2 clinical trials for latiglutenase, the celiac disease drug being developed by the company. A gluten challenge study done as part of the clinical trials revealed how little change there was in blood test levels when those on a gluten-free diet started consuming gluten again, and study authors presented the data because of its potential usefulness in diagnosis.

Blood tests rarely go from negative to positive

Twenty two study participants who were negative for tissue transglutaminase (TTG-IgA), one of the blood tests used to diagnose celiac disease, ate 2 grams of gluten every day for six weeks, for a total of 84 grams of gluten. Only two had their TTG blood tests go from negative to positive, the study found. Only about 23 percent of the 22 study participants had any positive change in any of the three types of celiac disease blood tests evaluated.

This raises concern that prescribing a gluten regimen to those suspected of having celiac disease to induce positive blood results as part of diagnosis may lead to unintended false negative results, the authors wrote. Re-introducing gluten into the diet does not immediately result in positive blood test results the findings of the study show, the company said in a press release.

“These findings will enable us to better monitor celiac disease and refine the tools we use in its diagnosis,” said Jack Syage, PhD., president and chief scientific officer of Entero.

How much gluten

In a brief report published in a special issue “Recent Advances in Gluten-Free Diet and Celiac Disease” in the journal Nutrients that is based on the data detailed in the poster, the study authors note that a negative celiac disease blood test can prevent a patient doing a gluten challenge from going on to have a biopsy to confirm celiac disease.

A 2011 gluten-challenge study by researchers from Finland cited in the report showed that moderate totals of gluten, from 145 to 412 grams, given in amounts of three to five grams for about one to three months, resulted in five of 10 study participants having blood test results that went from negative to positive blood tests.

While these results were not surprising, the authors wrote, “it is important to note from a diagnostic perspective that a large percentage of these gluten-challenged patients would have been classified as [celiac disease] negative on that basis alone.”

The American College of Gastroenterology recommends a gluten challenge of one to three slices of bread per day for one to three months. A slice of bread contains two to four grams of gluten.

Immunogenx was developing latiglutenase until the company was acquired by First Wave Bio Pharma in March. First Wave last week rebranded as Entero Therapeutics, a move the company said was made to reflect its focus on addressing unmet need in gastrointestinal health, including celiac disease. Latiglutenase has been extensively studied and has completed Phase 1 and Phase 2 clinical trials.

Measuring intestinal health

A second poster presentation by Entero at DDW detailed a scale that combines the measurement of damage in the small intestine, called villus-height-to-crypt-depth-ratio, with measurement of the density of intraepithelial lymphocytes.

Intraepithelial lymphocytes are T-cells found in the intestinal tract. T-cells are white blood cells that function as the body’s disease fighting soldiers and are part of coordinated immune system battle. In the case of celiac disease, these soldiers incorrectly read gluten peptides as the enemy, rally the immune response troops and go on the attack, with resulting destruction of the absorbing lining of the intestine.

The combined scale is designed to improve the sensitivity and accuracy of indicators measuring the health of the lining of the small intestine in celiac disease patients. Results suggest the combined scale may be more sensitive to changes in the tissue of the small intestinal lining than traditional measures.

The research outlined in both posters is key to a better understanding of the triggers and intestinal damage of celiac disease through quantification, James Sapirstein, chief executive officer of Entero, said in a press release. “By quantifying the amount of gluten required to elicit an adverse immune response and measuring the underlying tissue alterations that lead to celiac symptoms, we can better design our Phase 3 clinical trial and determine what constitutes meaningful change in disease severity in response to latiglutenase, our investigational therapeutic,” he noted.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW are sometimes preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed scientific journal. Studies selected to be presented at DDW go through a review process.


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