Dietary Factors and Mucosal Immune Response in Celiac Disease Patients Having Persistent Symptoms Despite a Gluten-free Diet.

Goals: The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients. Background: For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa. Study: We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD. The density of CD3(+) and gamma delta(+) intraepithelial lymphocytes (IELs), CD25(+) and FOXP3(+) regulatory T cells, and CD117(+) mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4 were evaluated in duodenal biopsies. Results: All subjects kept a strict GFD and had negative celiac autoantibodies and recovered mucosal morphology. The asymptomatic patients had higher mean fiber intake (20.2 vs. 15.2 g/d, P=0.028) and density of CD3(+) IELs (59.3 vs. 45.0 cell/mm, P=0.045) than those with persistent symptoms. There was a similar but nonsignificant trend in gamma delta(+) IELs (17.9 vs. 13.5, P=0.149). There were no differences between the groups in other parameters measured. Conclusions: Low fiber intake may predispose patients to persistent symptoms in celiac disease. There were no differences between the groups in the markers of innate immunity, epithelial stress or epithelial integrity. A higher number of IELs in asymptomatic subjects may indicate that the association between symptoms and mucosal inflammation is more complicated than previously thought.