In
celiac disease (CeD),
gluten activates adaptive immune cells that cause damage to the small intestinal mucosa. Histological evaluation of intestinal biopsies allows for grading of disease severity. CeD can effectively be treated with a life-long
gluten-free diet.
Gluten challenge of treated CeD patients is used to confirm diagnosis and to test
drug efficacy in clinical trials, but patients respond with different magnitudes to the same
gluten challenge. In this study of 19 well-treated CeD patients,
proteome analysis of total tissue or isolated epithelial cell compartment from
formalin-fixed
paraffin embedded biopsies collected before and after 14-day
gluten challenge demonstrates that patients with strong mucosal response to challenge have signs of ongoing tissue
inflammation already before challenge. This low-level tissue
inflammation at baseline is paralleled by increased
gluten specific CD4+ T-cell frequencies in the gut and presence of a low-level blood inflammatory profile. Thus, apparently well-treated CeD is frequently not entirely quiescent, with presence of low-grade
inflammation and antigluten immunity in the gut mucosa. Histology assessment alone appears insufficient to judge full recovery and gut mucosal healing of CeD patients. The findings raise a concern whether a seemingly proper
gluten-free diet is able to curb gut
inflammation in all CeD patients.