Celiac Blood Test Eliminates Need for Eating Gluten

Think your patient may have celiac disease? The harsh reality is that current diagnostic tests require patients to consume gluten for an accurate diagnosis, which poses challenges for individuals already avoiding gluten.

A more tolerable approach appears to be on the horizon. Researchers in Australia have developed a blood test that can identify celiac disease with high sensitivity and specificity, even without consuming gluten.

“This is a simple and accurate test that can provide a diagnosis within a very short time frame, without the need for patients to continue eating gluten and feeling sick, or to wait months for a gastroscopy,” Olivia Moscatelli, PhD candidate, Tye-Din Lab, Walter and Eliza Hall Institute and University of Melbourne, Parkville, Australia, told Medscape Medical News.

The study was published online on June 9 in Gastroenterology.

Most Cases Go Undiagnosed

Celiac disease is an autoimmune disorder triggered by gluten found in wheat, rye, and barley. The only available treatment is a strict, life-long gluten-free diet.

The global prevalence of celiac disease is estimated at around 1%-2%, with 50%-80% of cases either undiagnosed or diagnosed late. That’s because the current reliable diagnosis of celiac disease requires the intake of gluten, which may deter people from seeking a diagnosis.

In earlier work, the researchers, working with Robert Anderson, MBChB, BMedSc, PhD, now with Novoviah Pharmaceuticals, made the unexpected discovery that interleukin-2 (IL-2) spiked in the blood of people with celiac disease shortly after they ate gluten.

But would this signal be present when no gluten had been consumed?

The team developed and tested a simple whole blood assay measuring IL-2 release (WBAIL- 2) for detecting gluten-specific T cells to aid in diagnosing celiac disease.

They collected blood samples from 181 volunteers — 75 with treated celiac disease on a gluten-free diet, 13 with active untreated celiac disease, 32 with nonceliac gluten sensitivity and 61 healthy controls. The blood samples were mixed with gluten in a test tube for a day to see if the IL-2 signal appeared.

The WBAIL-2 assay demonstrated high accuracy for celiac disease, even in patients following a strict gluten-free diet.

For patients with HLA-DQ2.5+ genetics, sensitivity was 90% and specificity was 95%, with lower sensitivity (56%) for patients with HLA-DQ8+ celiac disease.

The WBAIL-2 assay correlated strongly with the frequency of tetramer-positive gluten-specific CD4+ T cells used to diagnose celiac disease and monitor treatment effectiveness, and with serum IL-2 levels after gluten challenge.

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 celiac disease might react to gluten, without them actually having to eat it,” Moscatelli said in a news release.

“Current diagnostic practice involves a blood-based serology test followed by a confirmatory gastroscopy if positive. Both tests require the patient to eat gluten daily for 6-12 weeks prior for accurate results. We envision the new blood test (IL-2 whole blood assay) will replace the invasive gastroscopy as the confirmatory test following positive serology,” Moscatelli told Medscape Medical News.

“In people already following a gluten-free diet, we propose they would have this new blood test done on two separate occasions and two positive results would be required for a celiac diagnosis. This would allow a large number of people who previously have been unable to go through the current diagnostic process to receive a diagnosis,” Moscatelli said.

Practice Changing Potential 

Blood-based test that can accurately detect celiac disease without the need for a gluten challenge would be “welcome and practice changing,” said Christopher Cao, director, Celiac Disease Program, Division of Gastroenterology, Mount Sinai Health System, New York City.

“A typical ‘gluten challenge’ involves eating the equivalent of 1-2 slices of bread daily for the course of 6 weeks, and this may be incredibly difficult for patients who have already been on a gluten-free diet prior to an official celiac disease diagnosis. Inability to perform a gluten challenge limits the ability to make an accurate celiac disease diagnosis,” Cao told Medscape Medical News.

“This study shows that gluten-stimulated interleukin release 2 assays may correlate with the presence of pathogenic gluten-specific CD4+ T cell response in celiac disease,” Cao noted.

He cautioned that “further large cohort, multicenter prospective studies are needed to assess generalizability and may be helpful in evaluating the accuracy of WBAIL-2 in non-HLA DQ2.5 genotypes.” 

Other considerations prior to implementation may include reproducibility across different laboratories and overall cost effectiveness, Cao said. “Ultimately in clinic, the role of WBAIL-2 will need to be better defined within the algorithm of celiac disease testing,” he added.

The Path Ahead

The researchers plan to test the performance of the IL-2 whole blood assay in a pediatric cohort, as well as in other countries to demonstrate the reproducibility of the test. In these studies, the test will likely be performed alongside the current diagnostic tests (serology and gastroscopy), Moscatelli told Medscape Medical News.

“There are some validation studies starting in other countries already as many celiac clinicians globally are interested in bringing this test to their clinical practice. I believe the plan is to have this as an approved diagnostic test for celiac disease worldwide,” she said.

Novoviah Pharmaceuticals is managing the commercialization of the test, and the plan is to get it into clinical practice in the next 2 years, Moscatelli said.

The research was supported by Coeliac Australia, Novoviah Pharmaceuticals (who provided the proprietary test for this study), Beck Family Foundation, Butterfield Family, the Veith Foundation. A complete list of author disclosures is available with the original article. Cao had no relevant disclosures.