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A laboratory test to detect gliadin-specific CD4+ T-cells for difficult to diagnose celiac disease
Daan A R Castelijn1,2, Nicolette J Wierdsma3, Kim de Buck1
1Department of Laboratory Medicine, Laboratory Specialized Diagnostics and Research, Section Medical Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Insights
Diagnosing celiac disease (CD) can be challenging. A new method simplifies detecting gliadin-specific T-cells in blood, aiding difficult CD cases and improving gluten sensitivity diagnosis.
Area of Science:
- Immunology
- Gastroenterology
- Diagnostics
Background:
- Serological and histological discrepancies complicate celiac disease (CD) diagnosis, particularly in seronegative cases.
- Existing methods for detecting gliadin-specific T-cells are often too labor-intensive for routine use.
- A need exists for a more accessible diagnostic tool for celiac disease.
Purpose of the Study:
- To develop and validate a simplified method for detecting gliadin-specific T-cells.
- To assess the utility of this method in diagnosing celiac disease, including challenging cases.
- To evaluate the impact of a gluten challenge on T-cell detection.
Main Methods:
- Analysis of gliadin-specific T-cells using α1- and α2-gliadin peptide-loaded Dextramers (Dm) in healthy controls, non-celiac gluten sensitivity patients, active CD patients, and CD patients on a gluten-free diet (GFD).
- Calculation of the α-gliadin-Dm:CLIP-Dm ratio for background control.
- Implementation of a short-term gluten challenge in CD patients on a GFD to assess T-cell response.
Main Results:
- Significantly higher frequencies of gliadin-specific CD4+ T-cells were observed in active CD and GFD patients compared to controls (p ≤ 0.0001).
- Gliadin-specific T-cells were detected in most CD patients on GFD after a gluten challenge, with upregulation of CD38 observed.
- Real-world data confirmed the applicability of the simplified detection method in diagnostically challenging CD cases.
Conclusions:
- Commercially available dextramers can detect persistent gliadin-specific T-cells in celiac disease patients, even those on a GFD.
- A simplified detection method for gliadin-specific T-cells is suitable for challenging CD diagnoses.
- Short-term, low-dose gluten challenges can enhance the sensitivity of T-cell detection.
Objectives:
Discrepancy between serology and small bowel histology, such as seronegative CD, poses a diagnostic challenge in celiac disease (CD) diagnosis. Recently described methods to detect gliadin-specific T-cells are too laborious even in a specialized diagnostic setting. We developed a method, which can be implemented in specialized diagnostic laboratories.
Methods:
Gliadin-specific T-cells were analyzed by α1-and α2-gliadin peptide loaded Dextramers (Dm) in healthy controls (HC, n = 18), patients with non-celiac gluten sensitivity (NCGS, n = 9), active CD (aCD, n = 7) and CD on a gluten free diet (GFD, n = 14). Control peptide (CLIP)-loaded Dm were used as background controls. The α-gliadin-Dm:CLIP-Dm ratio was calculated. In CD patients ≥5 years on GFD (n = 8), a randomized two-dose gluten challenge was performed to increase gliadin-specific T-cell frequencies.
Results:
Gliadin-specific CD4+ T-cell frequencies were significantly higher in aCD and GFD than in HC and NCGS (p ≤ 0.0001). In CD patients on a GFD ≥5 years, gliadin-specific T-cells were detectable in 6/8 patients after a week gluten challenge, and all tested positive within 4 weeks. Gliadin-specific T-cells significantly upregulated CD38 after 1 week of gluten ingestion (p < 0.008). Real world data from sixteen patients demonstrated the applicability of this test in diagnostic challenging cases.
Conclusions:
Gliadin-specific T-cells can be detected in peripheral blood of CD patients using commercially available dextramers. These cells persist in CD patients on a GFD but may decline over time. A short term low-dose gluten challenge increased sensitivity. This simplified detection method of gliadin-specific T-cells is suitable for diagnostic challenging CD cases.
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