Purified oat protein can trigger acute symptoms linked to immune activation in coeliac disease patients but not histological deterioration

Abstract

Background: Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals.

Objective: To correlate immune and clinical outcomes to oats, purified avenin and oat feeding studies were performed to examine symptoms, T-cell immunity and intestinal histology in CD.

Design: 33 treated HLA-DQ2.5+ adult CD patients underwent single-bolus or 6-week oat avenin or 3-month whole oats ingestion. T cell activation after avenin ingestion was measured using serum interleukin 2 (IL-2), a sensitive and specific biomarker of gluten-induced T cell activation and symptoms in CD. Symptom measures, intestinal histology, and immune studies on blood and duodenum were undertaken.

Results: Among 29 CD participants, avenin induced dose-dependent T-cell activation in 11 (38%) and acute symptoms in 17 (59%). Higher IL-2 levels correlated with more severe symptoms. A single highly symptomatic patient vomited in response to avenin (1/29; 3%) and exhibited a striking pro-inflammatory cytokine profile similar to wheat-induced responses. Avenin increased the frequency of CD38-expressing tetramer+integrin β7+ T effector memory CD4+ T cells in the blood, however symptoms, IL-2 release and tetramer frequency fell following 6-week avenin intake and no enteropathy was observed.

Conclusion: Gluten-contamination-free oats can trigger acute dose-dependent immune and symptom responses but usually at a level insufficient to cause sustained symptoms or enteropathy. In 1 of 29 (3%) participants, oat avenin triggered a pro-inflammatory wheat-like response, highlighting that a minority of CD patients may need to exclude oats. Informed choice regarding oats ingestion in CD is important.

Keywords: COELIAC DISEASE; CYTOKINES; GLUTEN; INTESTINAL T CELLS.