Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis

Abstract

To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease, which is specifically expressed in cytotoxic lymphocytes, in different types of chronic inflammation of the gastric mucosa. Gastric and duodenal biopsies of patients with Helicobacter pylori (H pylori)-associated active gastritis (Hp, n = 19), chemically induced reactive gastritis (CG, n = 17), autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10), and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG. Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P<0.001) and significantly decreased for HP (0.7%, P<0.05). Double staining with anti-CD3 and anti-CatW antibodies revealed that >90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P<0.01). The corresponding proportion of CatW/CD45-postive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P<0.05). The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.