Live Webinar: Detection of gliadin specific T-cells for diagnosis of challenging cases of celiac disease

This webinar will cover: 

• Introduction to studying CD4+ T cells  

• Analysis of gliadin-specific T cells for diagnosis of celiac disease   

• Results of a randomized two-dose gluten challenge study in celiac disease patients  

Abstract  

Celiac disease (CD) is chronic enteropathy caused by an inappropriate immune response to gluten peptides leading to duodenal lymphocytosis, crypt hyperplasia and villous atrophy. The first diagnostic step is determination of IgA-antibodies against tissue transglutaminase (tTG-IgA) which has a high diagnostic accuracy for CD diagnosis.  

If CD diagnosis is confirmed, patients are treated with a lifelong gluten-free diet (GFD). After introduction of a GFD, tTG-IgA antibodies will drop to below detection level and intestinal damage will resolve. Therefore, self-initiation of a GFD will decrease the accuracy of CD diagnosis as routine diagnostics are no longer useful. This self-initiated gluten elimination is increasingly prevalent in individuals without confirmed CD diagnosis. GFD in non-CD individuals can cause health-risks as gluten-free products often contain less fibers and vitamins but more fat and sugar. Furthermore, CD is associated with other auto-immune diseases and complications such as iron deficiency and osteoporosis, which require additional testing and regular follow-up.  

Current guidelines suggest a 2-6 weeks high dose gluten challenge to re-induce serological and histological abnormalities in cases suspect for CD on a GFD, but this is burdensome for patients, has poor compliance and low diagnostic accuracy. Therefore, novel diagnostic strategies are needed to adequately and rapidly distinguish CD patients from individuals with other gluten-related complaints.  

Gliadin-specific T-cells have been suggested as a diagnostic marker, but the current detection method is less suitable for routine diagnostics. We therefore simplified this method using Dextramer® reagents (Dm). PBMC from healthy controls (n=10), patients with non-celiac gluten sensitivity (NCGS; n=9), active CD (ACD, n=7) and CD on GFD (GFD, n=14) were analyzed. Gliadin-specific T-cells were analyzed by α1- and α2-gliadin peptide loaded Dm, 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 circulating gliadin-specific T-cells. Results and implications of this study will be discussed.