Blood-Based T-Cell Diagnosis of Celiac Disease

Abstract

Background & Aims Current diagnosis of celiac disease (CeD) is inaccurate in patients following a gluten-free diet (GFD). Blood-based diagnostics targeting gluten-specific T cells, like 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 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 on GFD, 13 consuming gluten) and 93 controls (32 on GFD with non-celiac gluten sensitivity, 61 healthy). In vitro IL-2 release in whole blood after gluten peptide stimulation was measured. The assay's performance was compared to tetramer-based methods, and serum IL-2 levels were monitored before and after a single-dose gluten challenge. Correlations between IL-2 levels, tetramer+ T-cell frequencies, and symptoms were examined. Results The WBAIL-2 assay demonstrates high accuracy for CeD diagnosis, even in patients following a strict GFD. Optimized dual cut-offs 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+ gluten-specific CD4+ T cells and serum IL-2 levels after gluten challenge. Elevated WBAIL-2 levels predicted gluten-induced symptom severity, such as vomiting. The assay required only small blood volumes and performed comparably to 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.

Topics & Concepts