[Celiac disease; a world in exploration]. / La celiachia: un mondo in esplorazione.

Celiac disease (CD) or gluten-sensitive enteropathy is an autoimmune disorder triggered by gluten ingestion in genetically predisposed subjects. The presence of gluten in these patients leads to a self-perpetuating mucosal damage, while the elimination of gluten results in a full mucosal recovery. The prevalence of CD in the general population is between 0.3% and 1%. The clinical manifestation of CD is variable; in addition to the classical gastrointestinal form a variety of other clinical manifestation of the disease have been described, including atypical and asymptomatic form. The diagnosis of CD is still based on the small intestinal biopsy findings, but can be suspected using serological testing, e.g. the antigliadin antibody (AGA), the antiendomysial antibody (EMA) and the anti-tissue transglutaminase antibody (tTG). The keystone treatment of CD patients is a life-long gluten-free diet.

Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

BACKGROUND AND AIMS: Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. METHODS: The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. RESULTS: Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. CONCLUSIONS: Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.