Australian researchers hope a new test will change the landscape in diagnosing coeliac disease, saying that a new blood test for gluten-specific T cells has a high accuracy in diagnosing the disease, even when no gluten is eaten.
Their research suggested that coeliacs may soon no longer need to eat large amounts of gluten – the very thing suspected of making them sick – to get an accurate diagnosis.
The findings could help address “one of the biggest deterrents in current diagnostic practices”, they said in their findings, published in the journal Gastroenterology.
Around 1% of people in western countries have coeliac disease, the autoimmune condition in which gluten causes an inflammatory reaction in the small bowel, reports The Guardian.
Currently, every approved method to diagnose it requires people to eat gluten, the paper said. Testing methods – blood tests or a gastroscopy – require weeks of a person eating gluten, while often enduring symptoms such as diarrhoea, abdominal pain and bloating.
Despite the importance of early diagnosis, the researchers said many people are deterred because they do not want to get sick from the tests.
More than one in two cases of coeliac disease are either undiagnosed or diagnosed late, prior research has shown.
“There are probably millions of people worldwide living with undiagnosed coeliac disease simply because the path to diagnosis is difficult, and at times, debilitating,” said Associate Professor Jason Tye-Din, a senior author of the paper and head of the Coeliac Research Laboratory at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia.
The new research could help address one of the biggest deterrents in current diagnostic practices, he added.
The study evaluated the potential of a blood test to measure an immune marker interleukin 2 (IL-2). In 2019 WEHI researchers discovered that marker spiked in the bloodstream of coeliacs shortly after they ate gluten.
Researchers analysed blood samples from 181 volunteers between the ages of 18 and 75 recruited at Royal Melbourne Hospital.
These included 75 people with coeliac disease who had been on a gluten-free diet for at least a year, 13 with active, untreated coeliac disease, 32 with non-coeliac gluten sensitivity and 61 controls who had neither coeliac disease nor gluten sensitivity.
Using a new diagnostic system developed with Novoviah Pharmaceuticals, participant blood samples were mixed with gluten to see if the IL-2 signal appeared.
They found the test detected the condition with up to 90% sensitivity and 97% specificity – even in patients following a strict gluten-free diet, said lead author Olivia Moscatelli, who was diagnosed with coeliac disease at 18.
Novoviah Pharmaceuticals was an industry partner on the study, but played no role in the execution or interpretation of the research, authors said. The company aims to get the test into clinical use within two years.
The researchers acknowledged the limitations of the study in that it only involved participants from one centre with relatively small subgroup sizes, and that children and patients on immunosuppressants were not assessed.
Professor Peter Gibson, a gastroenterologist from Monash University, said further studies were needed, but “the science is of high quality, the numbers of people tested is large, their underlying conditions well described and the results are very impressive”.
“The test technically is simple so it can readily be adapted to a routine laboratory test,” he said, calling it a “genuinely major step forward in the diagnosis of coeliac disease at least in clinically uncertain circumstances”.
Associate Professor Vincent Ho, a gastroenterologist at the Western Sydney University’s School of Medicine, said the test needed to be validated across other laboratories and be cost-effective compared with current tests before it can be used in clinical practice.
He said one of the most accurate tests currently used to assess coeliac disease was the anti-endomysial antibody test, with 98% sensitivity and 98% specificity.
Ho noted the study’s small sample size and that it would be important the results be replicated in other larger studies in other centres.
“The research … showed that in patients with coeliac disease a single dose of gluten (10 grams or the equivalent of four slices of wheat bread) was able to result in an immune reaction that could be detected on a blood sample in the lab,” he added.
“This means in theory that coeliac disease could be diagnosed without the need for weeks of exposure to gluten.”
But, Ho said, because the test assesses an immune response to gluten, this means that people on immunosuppressive drugs may not register a reaction.
Study details
Blood-based T Cell Diagnosis of Celiac Disease
Olivia Moscatelli, Amy Russell, Lee Henneken et al.
Published in Gastroenterology Journal on 9 June 2025
Abstract
Background & Aims
Current diagnosis of celiac disease (CeD) is inaccurate in patients following a gluten-free diet (GFD). Blood-based diagnostics targeting gluten-specific T cells, like tetramer assays, are highly sensitive and specific but are impractical for clinical use. We evaluated the potential of a simple whole blood assay measuring interleukin-2 release (WBAIL-2) for detecting gluten-specific T cells to aid in CeD diagnosis.
Methods
WBAIL-2 was assessed in 181 adults; 88 with CeD (75 on GFD, 13 consuming gluten) and 93 controls (32 on GFD with non-celiac gluten sensitivity, 61 healthy). In vitro IL-2 release in whole blood after gluten peptide stimulation was measured. The assay’s performance was compared to tetramer-based methods, and serum IL-2 levels were monitored before and after a single-dose gluten challenge. Correlations between IL-2 levels, tetramer+ T-cell frequencies, and symptoms were examined.
Results
The WBAIL-2 assay demonstrates high accuracy for CeD diagnosis, even in patients following a strict GFD. Optimised dual cut-offs in HLA-DQ2.5+ patients showed high sensitivity (90%) and specificity (95%), with lower sensitivity (56%) in HLA-DQ8+ CeD. WBAIL-2 correlated strongly with the frequency of tetramer+ gluten-specific CD4+ T cells and serum IL-2 levels after gluten challenge. Elevated WBAIL-2 levels predicted gluten-induced symptom severity, such as vomiting. The assay required only small blood volumes and performed comparably to tetramer-based methods.
Conclusions
Gluten-stimulated IL-2 secretion indicates the presence of pathogenic gluten-specific CD4+ T cells and is a useful diagnostic for CeD. WBAIL-2 and serum IL-2 after gluten could be complementary and allow biopsy-free CeD diagnosis. WBAIL-2 may help diagnose and monitor other CD4+ T cell-driven diseases.
Gastroenterology article – Blood-based T Cell Diagnosis of Celiac Disease (Open access)
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