Blood-Based T-Cell Diagnosis of Celiac Disease

Moscatelli, OG; Russell, AK; Henneken, LM; Fothergill, L; Motyer, A; Reid, H; Rossjohn, J; Bryant, V; Anderson, RP; Hardy, MY; Tye-Din, JA

Author(s): Moscatelli, OG; Russell, AK; Henneken, LM; Fothergill, L; Motyer, A; Reid, H; Rossjohn, J; Bryant, V; Anderson, RP; Hardy, MY; Tye-Din, JA;
Details: Publication Year 2025-11,Volume 169,Issue #6,Page 1253-1267 e5
Journal Title: Gastroenterology
Abstract: BACKGROUND & AIMS: Current diagnosis of celiac disease (CeD) is inaccurate in patients consuming a gluten-free diet (GFD). Blood-based diagnostics targeting gluten-specific T cells, such as 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 (IL-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 consuming a GFD, 13 consuming gluten) and 93 controls (32 consuming a GFD with nonceliac gluten sensitivity, 61 healthy). In vitro IL-2 release in whole blood after gluten peptide stimulation was measured. The assay's performance was compared with tetramer-based methods, and serum IL-2 levels were monitored before and after a single-dose gluten challenge. Correlations between IL-2 levels, tetramer-positive T-cell frequencies, and symptoms were examined. RESULTS: The WBAIL-2 assay demonstrates high accuracy for CeD diagnosis, even in patients consuming a strict GFD. Optimized dual cutoffs 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-positive gluten-specific CD4(+) T cells and serum IL-2 levels after a gluten challenge. Elevated WBAIL-2 levels predicted gluten-induced symptom severity, such as vomiting. The assay required only small blood volumes and performed comparably with 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.
Publisher: Elsevier
Keywords: Humans; *Celiac Disease/diagnosis/immunology/blood/diet therapy; *Interleukin-2/blood; Adult; Glutens/immunology; Male; Female; Middle Aged; Diet, Gluten-Free; *T-Lymphocytes/immunology; Aged; Biomarkers/blood; Young Adult; HLA-DQ Antigens; Case-Control Studies; Predictive Value of Tests; Celiac Disease; Diagnostics; Interleukin-2; T cells
Research Division(s): Immunology; Advanced Technology and Biology
PubMed ID: 40499737
Publisher's Version: https://doi.org/10.1053/j.gastro.2025.05.022
Open Access at Publisher's Site: https://doi.org/10.1053/j.gastro.2025.05.02
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-26 09:55:22

Last Modified: 2025-11-03 09:25:15