A newly developed blood test that detects gluten-specific immune responses offers a simpler, more accurate alternative to invasive procedures for diagnosing celiac disease, even in patients on a gluten-free diet.
Study: Blood-based T Cell Diagnosis of Celiac Disease. Image Credit: Kmpzzz/Shutterstock.com
A recent study published in Gastroenterology introduces a new blood-based test that measures interleukin-2 (IL-2) release after gluten exposure—offering a simpler and less invasive option for diagnosing celiac disease. Known as the whole blood IL-2 release assay (WBAIL-2), the test could be especially helpful for patients already on a gluten-free diet (GFD) or those hesitant to undergo an endoscopy.
Background
Celiac disease (CeD) is an autoimmune disorder where the immune system reacts to gluten, damaging the small intestine. Despite ongoing research, diagnosing CeD remains difficult, particularly for individuals who have started a GFD, which can mask traditional diagnostic markers. The standard approach typically involves small intestinal biopsies, a process that’s both invasive and not always definitive.
Because gluten-specific CD4+ T cells play a central role in CeD, researchers have looked to cytokine release—specifically IL-2—as a practical biomarker of immune activation. IL-2 is released when these T cells are stimulated by gluten, and this response can be measured using a blood sample. Previous studies suggested that IL-2 could be a reliable indicator of gluten-specific immune activity.
The Study
This new study assessed WBAIL-2 in 181 adults, including patients with active celiac disease (both on and off a GFD), healthy individuals, and those with non-celiac gluten sensitivity. Blood samples were stimulated in the lab with gluten peptides, and IL-2 levels were measured using ELISA or a similar sensitive method. The team fine-tuned the test for accuracy, checking how results held up across different users and repeated trials.
Researchers compared WBAIL-2 against tetramer-based techniques (which identify gluten-specific T cells directly) and serum IL-2 levels before and after a gluten challenge, a controlled gluten exposure used to provoke a measurable immune response. They also analyzed results by genetic background, focusing on HLA-DQ2.5 and HLA-DQ8 genotypes, which are strongly linked to celiac disease risk.
Results and Discussion
WBAIL-2 showed high diagnostic accuracy, even in patients who were already avoiding gluten. In those with the HLA-DQ2.5 genotype, sensitivity reached around 90 % and specificity approached 95 %. The assay performed slightly less well in HLA-DQ8 carriers but still showed strong potential.
Importantly, IL-2 levels matched well with the presence of gluten-specific T cells and even correlated with physical symptoms like vomiting during a gluten challenge. This suggests the test may not only detect immune reactivity but also reflect the severity of a patient’s response.
WBAIL-2 also proved to be consistent and reproducible, with low variability between users and across different testing rounds. Its ability to detect gluten reactivity from small blood volumes adds to its appeal, particularly for pediatric use.
The researchers suggest WBAIL-2 could complement or even replace current diagnostic steps in some cases, especially for patients already on a GFD or with unclear biopsy results.
Conclusion
The study provides strong evidence that the whole blood IL-2 release assay is a reliable, non-invasive option for diagnosing celiac disease. With high accuracy, ease of use, and applicability to small blood samples, WBAIL-2 could become an important tool in clinical practice. It may help improve diagnostic confidence, especially in tricky cases where traditional methods fall short.
Future research will be key to confirming its use across broader populations, but the early data is encouraging. The potential to simplify diagnosis and tailor care more precisely makes WBAIL-2 a test to watch.
Journal Reference
Moscatelli O.G., Russell A.K., et al. (2025). Blood-based T Cell Diagnosis of Celiac Disease. Gastroenterology. DOI: 10.1053/j.gastro.2025.05.022. https://www.sciencedirect.com/science/article/pii/S0016508525008327?via%3Dihub