Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease.
OBJECTIVE
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.
Montalto
Massimo
M
Institute of Internal Medicine, Catholic University, Rome, Italy. mmontalto@rm.unicatt.it
Cuoco
Lucio
L
Ricci
Riccardo
R
Maggiano
Nicola
N
Vecchio
Fabio Maria
FM
Gasbarrini
Giovanni
G
D000328:Adult; D002446:Celiac Disease / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018753:Diet, Protein-Restricted; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005983:Glutens; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005983:Glutens