Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease

Abstract

Objective: Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed.

Design: 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14-day GC at a randomly assigned dose of 3 or 7.5 g of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tissue transglutaminase and deamidated gliadin peptides, lactulose to mannitol ratio (LAMA) and symptoms were assessed at each visit.

Results: Significant reduction in Vh:Cd (2.2-1.1, p<0.001) and increase in IELs (32.6-51.8, p<0.001) were seen from baseline to day 14. Antibody titres increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses.

Conclusions: 14 day GC at ≥ 3 g of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a 2-week GC.

Trial registration: ClinicalTrials.gov NCT00931892.

Keywords: Coeliac disease; gluten challenge; histology; symptoms; transglutaminase.

Figures

Figure 1. Histologic parameters at baseline and on Day 3 and Day 14 of gluten challenge

a: Villous Height to Crypt Depth Ratio; b: Intraepithelial Lymphocyte Count per 100 Enteroctyes; c: Villous Height to Crypt Depth Ratio in Low and High Gluten Dose Groups; d: Intraepithelial Lymphocyte Count per 100 Enteroctyes in Low and High Gluten Dose Groups.

Figure 2. Mean antibody titers from Baseline through Day 28

a: IgA anti-tTG; b: IgA anti-DGP, IgG anti-DGP and IgA/IgG anti-DGP; c: IgA anti-tTG in Low and High Gluten Dose Groups; d: IgA/IgG anti-DGP in Low and High Gluten Dose Groups.

Figure 3 a-b. Mean Lactulose to Mannitol Ratios from Baseline through Day 28

a: from Baseline through Day 28; b: Low and High Gluten Dose Groups.

Figure 4 a-b. Symptom Index Scores from Baseline through Day 28

a: Celiac Symptom Index Scores; b: Gastrointestinal Symptom Rating Scale Scores; c: Celiac Symptom Index Scores in Low and High Gluten Dose Groups.

Figure 5. Proposed Modified Gluten Challenge Algorithm