EXPRESSION OF TUMOR-ASSOCIATED THOMSEN-FRIEDENREICH ANTIGEN (T Ag) INHELICOBACTER PYLORIAND MODULATION OF T Ag SPECIFIC IMMUNE RESPONSE IN INFECTED INDIVIDUALS

Abstract

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.

Impact ofHelicobacter pyloriInfection on the Humoral Immune Response to MUC1 Peptide in Patients with Chronic Gastric Diseases and Gastric Cancer

“…The expression of TF epitope in H. pylori cell surface membrane glycoconjugates was demonstrated immunochemically (Klaamas et al, 2002a), suggesting that this may be one of the reasons for the up-regulation of TF specific immune response in H. pylori infected individuals. Recently we demonstrated a positive correlation between the levels of MUC1 IgG and TF epitope specific IgG antibodies in patients with early gastric cancer.…”

“…Determination of the CagA status was performed in patients with benign gastric diseases (n = 124) with immunoblotting as described elsewhere (Klaamas et al, 1996(Klaamas et al, , 2002a. Patients with CagA +/− results were not included in this study.…”

Increased Sialylation of Anti-Thomsen-Friedenreich Antigen (CD176) Antibodies in Patients with Gastric Cancer: A Diagnostic and Prognostic Potential

“…The origin of these Abs is still a matter of debate, but it appears that some of them (anti-TF and anti-alpha Gal Abs of different isotypes) are directed against microbial glycans or antigens cross-reactive with them [32–34]. Since the 1980s [1] it has been established that the level of anti-TF IgM is lower in cancer patients and is related to higher breast cancer risk.…”

Cancer vaccines and carbohydrate epitopes

“…TF-Ag was discovered due to the ubiquitous presence of antibody to this antigen in most human serum [95,96,162]. TF-Ag was exposed in bacterially contaminated red blood cells, and when the scientist attempted to determine the ABO blood group of the individual, all the sera caused hemagglutination.…”