New coeliac disease test removes need for gluten consumption

Current diagnostic tests for coeliac disease require people to eat large amounts of gluten — the thing that makes them sick — for weeks in order to get an accurate diagnosis. Now, researchers at the Walter and Eliza Hall Institute (WEHI) and Novoviah Pharmaceuticals have developed a landmark blood test that can identify the condition in patients — even when they’re on gluten-free diets.

Coeliac disease is one of the most common autoimmune illnesses in Australia, caused by an immune reaction to the gluten protein found in wheat, rye and barley. While early diagnosis is critical to minimising long-term complications of the disease, up to 80% of cases around the world remain undiagnosed.

The diagnostic process can be confusing, as the reduction in symptoms from a gluten-free diet is not always a marker of coeliac disease. Furthermore, current coeliac testing methods do not work reliably for those on a gluten-free diet, and require regular gluten consumption to be effective. As a result, many people are deterred from seeking a definite diagnosis because they do not want to consume gluten and feel sick.

“There are likely millions of people around the world living with undiagnosed coeliac disease simply because the path to diagnosis is difficult and, at times, debilitating,” said Associate Professor Jason Tye-Din, Head of WEHI’s Coeliac Research Lab and a gastroenterologist at The Royal Melbourne Hospital.

In 2019, WEHI researchers, working with Dr Robert Anderson (who went on to co-found Novoviah Pharmaceuticals), discovered that the immune marker interleukin 2 (IL-2) spiked in the bloodstream of people with coeliac disease shortly after they ate gluten. But could this critical signal still appear, even if no gluten had been consumed? Building on a promising pilot study in 2021, and using a new clinical diagnostic system developed with Novoviah Pharmaceuticals, the research team set out to test the performance and understand the science of an ‘in-tube’ gluten challenge blood test.

In their new study, published in the journal Gastroenterology, the researchers used blood samples from 181 volunteers recruited via The Royal Melbourne Hospital. This included 75 people with treated coeliac disease (on a gluten-free diet); 13 people with active, untreated coeliac disease; 32 people with non-coeliac gluten sensitivity; and 61 healthy controls. Participant blood samples were then mixed with gluten in a test tube for a day to see if the IL-2 signal appeared.

PhD researcher Olivia Moscatelli, who was diagnosed with coeliac disease at 18, said the team was thrilled to find the test could detect the condition with up to 90% sensitivity and 97% specificity — even in patients following a strict gluten-free diet.

“This breakthrough is deeply personal as it could spare others from the gruelling diagnostic process I had to endure,” Moscatelli said. “Knowing I’ve played a role in this achievement is a powerful, full-circle moment.”

As seen in the previous study, the IL-2 signal only increased in the volunteers with coeliac disease, demonstrating the immune response to gluten can be detected in a tube, without a gluten challenge. The test thus represents a promising new tool to support diagnosis, Moscatelli said — especially for people who can’t be diagnosed with the currently available methods.

“We also found the strength of the IL-2 signal correlated with the severity of a patient’s symptoms, allowing us to predict how severely a person with coeliac disease might react to gluten, without them actually having to eat it,” she added.

Moscatelli noted that some diagnostic tests give false positives in the presence of other autoimmune diseases, such as type 1 diabetes or Hashimoto’s thyroiditis, but this was not an issue.

“This is largely because the technology we use is highly sensitive and can detect the IL-2 signal at exceptionally low levels,” she said. “It’s like the equivalent of being able to detect a single grain of sand in a swimming pool.”

While the ultrasensitive cytokine testing technology used for this study isn’t currently utilised in pathology labs, the researchers hope this will change in the future, which would allow the blood test to be widely used by healthcare professionals. The WEHI team is now collaborating with Novoviah Pharmaceuticals to confirm the test’s accuracy across diverse populations and accrue real-world data.

“This test could be a game changer, sparing thousands of people the emotional and physical toll of returning to gluten,” Tye-Din said. “It’s a major step towards faster, safer diagnosis.”

Image courtesy WEHI