Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease

Digestion. 2002;65(4):227-33. doi: 10.1159/000063817.


Background/aim: ZO-1 is a good marker for tight junction integrity which may be damaged in many intestinal diseases. ZO-1 can also accumulate in the cellular nucleus in addition to sites of cell-cell contact, suggesting a potential role in cellular proliferation and differentiation. We evaluated the expression and distribution of ZO-1 in patients with celiac disease before and after a gluten-free diet.

Methods: The ZO-1 expression was evaluated semiquantitatively by means of immunohistochemical analysis in duodenal bioptic specimens of 10 consecutive patients with celiac disease before and after a gluten-free diet and in 10 controls. Furthermore, the nuclear staining was analyzed quantitatively, evaluating 3,000 cells for each count, and it was expressed as a percentage of labeled nuclei over the total of analyzed cells.

Results: The intestinal mucosa of untreated celiac disease patients shows a globally lower ZO-1 labeling than that of controls. The expression of ZO-1 in the treated celiac mucosa did not differ significantly from normal intestinal mucosa of healthy subjects. At the crypt level of untreated celiac mucosa, a low intensity of nuclear labeling (1.75 +/- 0.32%) was found, while in both treated celiac disease patients and in normal subjects we observed a statistically significant higher percentage of strongly labeled nuclei (53.72 +/- 6.30% and 56.79 +/- 5.45%, respectively; p = 0.0002).

Conclusions: Our data show a global underexpression of ZO-1 in the duodenal mucosa of active celiac disease patients. Gluten withdrawal allows a normalization of the ZO-1 expression in treated celiac disease patients. Furthermore, the particular pattern of ZO-1 resembles the cellular distribution in undifferentiated cells and may be the result of immaturity of the enterocytes in untreated celiac sprue.

MeSH terms

  • Adult
  • Celiac Disease / diet therapy
  • Celiac Disease / metabolism*
  • Celiac Disease / pathology
  • Celiac Disease / physiopathology
  • Diet, Protein-Restricted
  • Duodenum / metabolism*
  • Duodenum / pathology
  • Duodenum / physiopathology
  • Female
  • Glutens
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Phosphoproteins / metabolism*
  • Zonula Occludens-1 Protein


  • Membrane Proteins
  • Phosphoproteins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Glutens