A NOVEL blood-based assay could transform coeliac disease (CeD) diagnosis, particularly for patients already on a gluten-free diet (GFD), by offering a minimally invasive, accurate, and practical alternative to current methods.
Conventional CeD diagnostics often fail when patients have begun a GFD, as gluten-specific T cells diminish and biopsies become unreliable. While tetramer assays offer high sensitivity and specificity by detecting gluten-reactive CD4+ T cells, their complexity limits clinical use. In this study, researchers investigated a novel whole blood assay measuring IL-2 release (WBAIL-2) as a more accessible alternative. The assay was tested on 181 adults: 88 with confirmed CeD (75 on GFD), 93 controls including those with non-coeliac gluten sensitivity and healthy individuals. IL-2 secretion was measured after gluten peptide stimulation and compared with tetramer-based methods. Researchers also analysed IL-2 levels before and after a single gluten challenge and assessed correlations with symptoms.
The WBAIL-2 assay demonstrated high diagnostic performance in HLA-DQ2.5+ individuals, achieving 90% sensitivity and 95% specificity. Although sensitivity was lower in HLA-DQ8+ CeD cases (56%), WBAIL-2 correlated strongly with tetramer+ T-cell frequencies and serum IL-2 levels post-gluten challenge. Notably, elevated IL-2 release was predictive of gluten-induced symptoms such as vomiting, suggesting clinical relevance beyond detection. The assay required only a small blood volume and matched the accuracy of the more complex tetramer approach.
This study highlights WBAIL-2 as a powerful tool for CeD diagnosis, even in patients adhering to a GFD. Its simplicity and accuracy support its potential use as a biopsy-free, front-line diagnostic and monitoring tool, with promise for broader application in other T cell-mediated diseases.
Reference
Moscatelli OG et al. Blood-based T cell diagnosis of celiac disease. Gastroenterology. 2025; DOI:10.1053/j.gastro.2025.05.022.
