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A small subset of those with celiac disease react to the protein in oat, study confirms

May 16, 2023

But no intestinal damage occurs and oats remain safe for most people with celiac disease

By Amy Ratner, director of scientific affairs

While oats are safe for most people with celiac disease, some patients react to the protein in oats with acute symptoms and a wheat-like inflammatory response, a study presented at Digestive Disease Week (DDW) found.

But even in those who reacted to the purified avenin protein in oats, no related intestinal damage was found as is the case when those with celiac disease consume gluten, according to the study. 

Exposure to the avenin protein in oats at levels sufficient to activate Interleukin 2 (IL-2) was not associated with intestinal damage after a six-week challenge and acute immunity fell over time, the study by researchers at several Australian institutions found. The results are preliminary and the study is continuing.

The research, presented by Melinda Hardy, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, is the first controlled immune study of avenin purified from uncontaminated oats. 

Those with celiac disease who do not react to uncontaminated oats can safely continue to include them in their gluten-free diets, said study author Jason Tye-Din, MD, also of the Walter and Eliza Hall Institute of Medical Research.

At the same time, the study results validate that there is a small subset of those with celiac disease who have both symptoms and a measurable immune reaction and need to avoid even uncontaminated oats, he said. “This shows the reaction is not all in their heads,” 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 journal. Studies selected to be presented at DDW go through a review process.

Oats safe for most with celiac disease

Purified oats that have not been cross contaminated by wheat gluten while being grown, transported or milled have long been thought to be safe for most of those with celiac disease patients. But the Australian researchers had noted that inflammatory T-cells specific to avenin had been isolated in the blood and intestinal tissue of those with celiac disease.

This finding raised troubling implications about the safety of oats for those who have celiac disease and led to the investigation of whether those susceptible to harm from oats could be identified.

Researchers said their results help resolve the discrepancy between clinical oats safety and oats immunity in celiac disease. Investigators wrote that it’s “reassuring” to have evidence that in most people with celiac disease, oats do not cause an immunological response at a level the results in damage to the intestine.  

How the study was done

Nearly 30 celiac disease patients, many of whom were experiencing symptoms after consuming uncontaminated oats, were included in the study. 

They were given a series of increasing doses of avenin, followed by an assessment of their symptoms and level of IL-2. Avenin is a water-soluble protein in oats similar to gluten protein in wheat, barley and rye. IL-2 is a sensitive marker of activation of T-cells, which are white blood cells that function as the body’s disease fighting soldiers. In the case of celiac disease, they are incorrectly turned on to attack when the gluten peptides are detected.

In results that researchers called “surprising,” acute IL-2 elevation was found in 11 of 29 study participants, nearly 40 percent, and 60 percent had pain, diarrhea and vomiting, with severity of these symptoms greater in those who had higher levels of IL-2. Tye-Din said the results were not representative of the general celiac disease population due to the large number of patients who chose to participate because of their sensitivity to oats. If the study participants were more representative of the celiac disease population, the numbers would be much lower, he said. 

Five study participants who had elevated IL-2 went on to have a six-week, daily avenin challenge at the highest tolerated dose that triggered IL-2.  Although they had an increase in T-cell response at first, after six weeks these had returned to baseline, with IL-2 response after avenin undetectable. Also, initial acute symptoms resolved. Overall, the avenin was well tolerated and symptoms were short lived after initial reactions.

The study says it is notable that after six weeks of challenge, intestinal biopsies were normal. This contrasted with results for a study participant who did a wheat gluten challenge for six weeks to serve as a control and experienced intestinal damage.

“For regulatory purposes oats should remain a priority allergen to support clear food labeling and informed dietary choices by celiac disease patients,” Hardy said.

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