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Blood-Based T-Cell Diagnosis of Celiac Disease
Olivia G Moscatelli1, Amy K Russell2, Lee M Henneken3
1Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Insights
A new whole blood assay measuring interleukin-2 (IL-2) release accurately detects celiac disease (CeD) in patients on a gluten-free diet. This simple test aids in diagnosing CeD by identifying gluten-specific T cells.
Area of Science:
- Immunology
- Gastroenterology
- Diagnostic Medicine
Background:
- Current celiac disease (CeD) diagnosis is challenging for patients on a gluten-free diet (GFD).
- Existing blood tests for gluten-specific T cells are sensitive and specific but not clinically practical.
- A simple whole blood assay measuring interleukin-2 (IL-2) release is proposed for CeD diagnosis.
Purpose of the Study:
- To evaluate a whole blood assay measuring IL-2 release (WBAIL-2) for detecting gluten-specific T cells in CeD diagnosis.
- To assess the diagnostic performance of WBAIL-2 in patients with and without CeD, including those on a GFD.
- To compare WBAIL-2 with established tetramer-based methods and monitor IL-2 levels after gluten challenge.
Main Methods:
- WBAIL-2 was performed on 181 adults (88 CeD, 93 controls).
- IL-2 release after in vitro gluten peptide stimulation was measured.
- Assay performance was compared to tetramer methods; serum IL-2 and symptoms were monitored post-gluten challenge.
Main Results:
- WBAIL-2 showed high accuracy for CeD diagnosis, including in patients on a GFD (90% sensitivity, 95% specificity in HLA-DQ2.5+).
- The assay strongly correlated with gluten-specific CD4+ T-cell frequency and serum IL-2 levels.
- Elevated WBAIL-2 predicted gluten-induced symptom severity and required minimal blood volume.
Conclusions:
- Gluten-stimulated IL-2 secretion indicates pathogenic gluten-specific CD4+ T cells, useful for CeD diagnosis.
- WBAIL-2 and serum IL-2 post-gluten challenge may enable biopsy-free CeD diagnosis.
- WBAIL-2 has potential for diagnosing and monitoring other CD4+ T cell-driven diseases.
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.
