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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kuester
Doerthe
D
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Leipziger Str. 44, Magdeburg 39120, Germany. thomas.wex@medizin.uni-magdeburg.de
Vieth
Michael
M
Peitz
Ulrich
U
Kahl
Stefan
S
Stolte
Manfred
M
Roessner
Albert
A
Weber
Ekkehard
E
Malfertheiner
Peter
P
Wex
Thomas
T
D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D016022:Case-Control Studies; D056664:Cathepsin W; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005756:Gastritis / Q000201:enzymology* / Q000276:immunology; D005757:Gastritis, Atrophic / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation
D017493:Leukocyte Common Antigens; D002403:Cathepsins; C534187:CTSW protein, human; D056664:Cathepsin W; D003546:Cysteine Endopeptidases