Localization of tissue transglutaminase and N (epsilon)-(gamma) -glutamyl lysine in duodenal cucosa during the development of mucosal atrophy in coeliac disease

Abstract

Expression and transamidation activity of tissue transglutaminase (tTG) may be involved in the morphological modifications leading to the mucosal atrophy observed in coeliac disease (CD). We aimed to investigate the localization of tTG within the duodenal mucosa during the development of villous atrophy. The localization and level of expression of N epsilon-(gamma-glutamyl) lysine isopeptides which could reflect the transamidation activity of tTG were also analyzed. tTG and N epsilon-(gamma-glutamyl) lysine were localized using an immunohistochemical technique on duodenal biopsies obtained from 75 patients with CD and 51 subjects with normal mucosa (control group). The number of cases displaying tTG-expressing cells in the basement membrane and lamina propria was significantly higher in CD patients than in the control group. Moreover, the intensity of tTG staining in these areas was higher in CD. In contrast, the number of biopsies with tTG-expressing enterocytes was significantly lower in CD than in the control group. There was no difference in N epsilon-(gamma-glutamyl) lysine between the two populations. Tissue transglutaminase was differently expressed in the various areas of the mucosa according to the stage of atrophy, whereas the localization and the intensity of the labelling of N epsilon-(gamma-glutamyl) lysine isopeptides did not show any modification. The preferential localization in the basement membrane and lamina propria may reflect the involvement of tTG in the development of mucosal atrophy in CD.

Tissue transglutaminase expression in celiac mucosa: an immunohistochemical study

“…It does not raise doubts that it can be found just beneath the epithelium, in lamina propria, and in the muscularis mucosae [16][17][18][19], but the data about its epithelial localization is conflicting. Some investigators have revealed epithelial tTG expression in normal duodenal mucosa [20], but the others have not [16,17,21]. We also have not found any significant epithelial tTG expression in most patients with normal duodenal mucosa except two cases with small focal areas of staining and believe that epithelial tTG expression is not usual for the normal duodenum.…”

“…We also have not found any significant epithelial tTG expression in most patients with normal duodenal mucosa except two cases with small focal areas of staining and believe that epithelial tTG expression is not usual for the normal duodenum. There is evidence from many studies conducted in the last 20 years that tTG is up-regulated in celiac mucosa [12][13][14], but till now, there exists some controversy concerning tTG distribution pattern in celiac mucosa and the source of its increased activity [11,17,19,20,22].…”

Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease

“…tTG-specific IgA deposits appear in the intestinal tissue of patients with CD in both the epithelium and the LP [8,28]. Although these deposits have been shown in the intestinal epithelium of individuals who are healthy or with other intestinal pathology [8,28], most studies found them to be significant only in CD [9,10,28].…”

“…Although these deposits have been shown in the intestinal epithelium of individuals who are healthy or with other intestinal pathology [8,28], most studies found them to be significant only in CD [9,10,28]. The detection of intestinal tTG-specific IgA deposits, as shown by immunohistochemical staining on frozen SBB specimens, was reported as a powerful diagnostic tool in detecting CD in patients with suspected disease and without villous atrophy [5].…”

“…Previous studies that examined correlations of antitTG serum level with intestinal morphology, or with clinical presentation and serology, showed contradictory results [5,8,9]. One study found that anti-tTG deposit measurement in intestinal tissue contributed to the prediction of the development of celiac disease in patients with clinically suspected disease but without villous atrophy [5].…”