Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?

Background & Aims: Crohn's disease (CD) is associated with a disturbed inte stinal barrier. Permeability studies have focused on inert molecules, but l ittle is known about transepithelial transport of macromolecules with antig enic potential in humans. The aim of this study was to quantify permeation and to characterize passage routes for macromolecules in ileal mucosa in CD . Methods: Noninflamed and inflamed ileal mucosa specimens from patients wi th CD (n = 12) and ileal specimens from patients with colon cancer (n = 7) were studied regarding transmucosal permeation of ovalbumin, dextran (mol w t, 40,000), and Cr-51-EDTA for 90 minutes in vitro in Ussing chambers. Tran sepithelial passage routes for fluorescent ovalbumin and dextran 40,000 wer e investigated by confocal microscopy. Results: Noninflamed ileum from CD p atients showed increased permeation of ovalbumin compared with ileum from c olon cancer patients (P < 0.05). Dextran permeation was equal in the three groups, whereas 51Cr-EDTA permeability was increased in in flamed ileum. Ov albumin passed both transcellularly and paracellularly, but dextran followe d a strictly paracellular route. Both markers were subsequently endocytosed by cells of the lamina propria. Conclusions: Noninflamed ileal mucosa from patients with CD shows increased epithelial permeability to ovalbumin, pro bably by augmented transcytosis. This increase in antigen load to the lamin a propria could be an initiating pathogenic event in CD.