Claudins expression in the proximal and distal parts of duodenum in patients with celiac disease

Abstract

Aims: Duodenal biopsy is an important method to diagnose celiac disease (CD), however, the most reliable location of biopsy site is questionable. Claudins (CLDN), members of adherent junction proteins, regulate the integrity and function of tight junctions in the intestinal mucosa. CLDN expression in CD is unknown. Aim: To examine whether proximal or distal part of duodenum is better in diagnosing villous atrophy in CD and to detect CLDN 2, 3, and 4 expressions in the proximal and distal parts of the duodenum in children with celiac disease and in controls. Patients and methods: 16 children (9 girls, mean age, 6.6 y, range, 2–17 y) with newly diagnosed CD were enrolled. Biopsies from proximal (duodenal bulb) and distal part (duodeno-jejunal junction) of duodenum were taken for histological analysis. Severity of mucosal atrophy were determined by means of Marsh-scoring system. Immunohistochemistry was used to detect CD3+ intraepithelial lymphocytes and CLDN 2, 3, and 4 protein expressions. Results: Macroscopic picture and histology, and Marsh grading depicted no differences between biopsies taken from proximal or distal parts, however, the densities of CD3+ intraepithelial T lymphocytes were significantly higher in distal duodenum in comparison to the proximal part (P=0.0064). CLDN 2 and 3 expressions were significantly elevated in the duodeno-jejunal junction compared with controls (P=0.0049), and with the proximal part. Moreover, CLDN 2 and 3 expressions were correlated with severity of villous atrophy. Expression of CLDN 4 protein was similar in all groups studied. Conclusions: Both proximal and distal mucosal duodenal biopsies are suitable for diagnosing villous atrophy in patients with CD, however, the distal part of duodenum depicted earlier signs of mucosal deterioration. Therefore, to diagnose slight changes of mucosal abnormality the distal duodenum seems to be better location for intestinal biopsies. Increased expressions of CLDN 2 and 4 suggest structural changes of tight-junction may be responsible for increased permeability and proliferation observed in CD.