Expression of tumor-associated Thomsen-Friedenreich antigen (T Ag) in Helicobacter pylori and modulation of T Ag specific immune response in infected individuals.
We tested the hypothesis that the gastric cancer associated bacteria, Helicobacter pylori (H. pylori) express the cancer-related Thomsen-Friedenreich (T) antigen. We also analysed whether infection with H. pylori alters the amount of natural anti-T antibodies in the patients' sera. Cell surface membrane extracts of H. pylori NCTC 11637 strain and clinical isolates of H. pylori (n = 13) were analysed by immunoblotting and cell-ELISA with five different T antigen-specific monoclonal antibodies (MAbs). Two major protein bands of approximately 68 kDa and 58 kDa were immunostained on blots of H. pylori extracts with T specific MAbs but not immunostained with unrelated MAb. The specificity was shown in that immunostaining was blocked with peanut agglutinin (PNA) and rabbit antiserum to T antigen. The binding of T specific MAb to the 58 kDa protein band was also blocked by rabbit antiserum against heat shock proteins of H. pylori. The relative expression of T antigen-related proteins differed among H. pylori strains, with 68 kD associated T antigen expression higher in patients with more severe pathology. The level of IgG antibody to T epitope in patients with gastric cancer (n = 66) and normal blood donors (n = 62) were compared and the level of anti-T Ab in gastric cancer patients was significantly lower than that in normal blood donors. A significant positive correlation between T specific antibody in serum and H. pylori IgG antibody level was found in H. pylori-infected normal blood donors (P < 0.001), but this correlation was not found in H. pylori-infected cancer patients. In summary, the cancer related T epitope is expressed in H. pylori and modulation of T antigen-specific immune response in H. pylori-infected individuals suggests that H. pylori infection may alter natural immune mechanisms against cancer.
Klaamas
Kersti
K
Institute of Experimental and Clinical Medicine, Hiiu 42, Tallinn 11619, Estonia.
Kurtenkov
Oleg
O
Rittenhouse-Olson
Kate
K
Brjalin
Vadim
V
Miljukhina
Ljudmila
L
Shljapnikova
Ljudmila
L
Engstrand
Lars
L
D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000032:analysis* / Q000737:chemistry; D000954:Antigens, Surface / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis* / Q000737:chemistry; D015153:Blotting, Western; D002277:Carcinoma / Q000276:immunology* / Q000382:microbiology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology; D006001:Glycoconjugates / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008970:Molecular Weight; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology
D000906:Antibodies; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D015295:Antigens, Tumor-Associated, Carbohydrate; D006001:Glycoconjugates; C016467:Thomsen-Friedenreich antigen; C025991:Thomsen-Friedenreich antibodies