Biopsy Proteome Score Performs Well as an Effect Measure in a Gluten Challenge Trial of Celiac Disease

Background and aims: Development of novel treatments for celiac disease is dependent on precise tools to monitor changes in gluten-induced mucosal damage. Current histology measures are subjective and difficult to standardize. Biopsy proteome scoring is an objective alternative to histology which is based on robust changes in biological pathways that directly reflect gluten-induced mucosal damage. In this study, we aimed to evaluate biopsy proteome scoring as an effect measure in a clinical trial setting by measuring intestinal remodeling in response to oral gluten challenge.

Methods: We analyzed biopsies from a 14-day gluten challenge trial of treated celiac disease patients that consumed 3 g (n = 6) or 10 g (n = 7) gluten per day. Sections from individually embedded biopsies collected before and after challenge were processed for proteome scoring (n = 109) and measurement of villus height-to-crypt depth ratio (n = 58). Proteome scores were compared with histology, intraepithelial lymphocyte frequency and plasma interleukin-2.

Results: Change in proteome scores were significant for the group of patients who consumed 10 g gluten, but not for the group who consumed 3 g gluten. Altogether, 8 of 13 patients had changes in delta proteome scores above the cutoff. Proteome scores correlated with villus height-to-crypt depth ratios both at run-in and at day 15. Proteome scores at day 15 correlated with intraepithelial lymphocyte frequency and with plasma interleukin-2 levels measured 4 hours post-gluten intake.

Conclusion: Biopsy proteome scoring is a simple and reliable measure of gluten-induced mucosal remodeling in response to 14-day oral gluten challenge.

Clinicaltrials: gov, Number: NCT03409796.