Impact of Helicobacter pylori infection on the humoral immune response to MUC1 peptide in patients with chronic gastric diseases and gastric cancer.

Many investigators have demonstrated alteration of gastric mucins in H. pylori infected individuals. The inflammatory environment induced by H. pylori leading to aberrant glycosylation of MUC1 and demasking of core peptide MUC1 epitope could enhance immune responses to MUC1. IgG and IgM immune response to MUC1 in patients with gastric cancer (n = 214) chronic gastroduodenal diseases (n = 160) and healthy blood donors (n = 91) was studied with ELISA using bovine serum albumin-MUC1 60-mer peptide as antigen. H. pylori serologic status was evaluated with ELISA and CagA status by immunoblotting. Gastric mucosa histology was scored according to the Sydney system. Compared to H. pylori seronegative individuals, higher levels of IgG antibody to MUC1 were found in H. pylori seropositive patients with benign gastric diseases (p < 0.01) and blood donors (p < 0.03). Higher MUC1 IgG antibody levels were associated with a higher degree of gastric corpus mucosa inflammation in patients with chronic gastroduodenal diseases (p < 0.0025). There was a positive correlation between the levels of anti-H. pylori IgG and MUC1 IgG antibody levels in blood donors (p = 0.03), and in patients with benign diseases (p < 0.0001). In patients with gastric cancer (n = 214) a significantly higher level of anti-MUC1 IgG than in blood donors was observed (p < 0.001) irrespective of H. pylori status or stage of cancer. MUC1 IgM antibody levels were not related to the H. pylori serology. IgG immune response to tumor-associated MUC1 is up regulated in H. pylori infected individuals. This increase is associated with a higher IgG immune response to H. pylori and with a higher degree of gastric mucosa inflammation. High levels of MUC1 IgG antibody irrespective of H. pylori serologic status characterized patients with gastric cancer. The findings suggest that, in some individuals, the H. pylori infection may stimulate immune response to tumor-associated MUC1 peptide antigen thus modulating tumor immunity.

Humoral immune response to MUC1 and to the Thomsen-Friedenreich (TF) glycotope in patients with gastric cancer: relation to survival.

Humoral immune responses to the MUC1 peptide and to MUC1-related Thomsen-Friedenreich (TF) glycotope was investigated in patients with gastric cancer (n = 247), chronic gastroduodenal diseases (n = 199) and in healthy blood donors (n = 100). Data were correlated with disease type, stage of cancer, tumor morphology and survival. MUC1 IgG antibody levels were higher in patients with gastric cancer (p < 0.0001) than in healthy controls. Higher levels of anti-MUC1 IgG were also detected in patients with ulcer of the stomach (p = 0.015) and in atrophic gastritis (p = 0.027). Compared to blood donors, significantly lower levels of anti-TF IgG were found both in the cancer (p = 0.002) and in the benign group (p < 0.0001). At early stages of cancer a positive correlation (p < 0.0001) was found between MUC1 IgG and TF IgG antibody levels. High levels of TF IgG antibodies were significantly associated with a benefit in survival of gastric cancer patients (p = 0.003). A similar though weaker association was observed for patients with high levels of MUC1 IgG antibodies and locoregional disease (stage I-III) (p = 0.037). Thus IgG immune responses to MUC1 are increased in patients with gastric cancer. High levels of either TF IgG or MUC1 IgG antibodies may predict better outcome in surgically treated patients with gastric cancer.

IgG immune response to tumor-associated carbohydrate antigens (TF, Tn, alphaGal) in patients with breast cancer: impact of neoadjuvant chemotherapy and relation to the survival.

AIM: To study the humoral immune response to tumor-associated carbohydrate epitopes (TF, Tn and alphaGal) in patients with breast cancer and healthy donors, the putative impact of the chemotherapy and to evaluate if the level of antibody to these epitopes might be beneficial or detrimental for the patients with breast cancer. MATERIALS AND METHODS: The humoral immune response to TF, Tn and alphaGal was studied in 133 patients with breast cancer, including the patients at stage II-III (n = 44) before and after neoadjuvant chemotherapy (10 patients received cyclophosphamide/methotrexate/fluorouracyl (CMF) chemotherapy regimens, 34 patients received cyclophosphamide/doxorubicin/fluorouracil (CAF)), and in controls (healthy donors and patients with fibroadenoma). Fully synthetic carbohydrate hapten-polyacrylamide conjugates were used as antigens in ELISA for anti-carbohydrate antibody determination. The correlation analysis between the level of anti-carbohydrate antibodies and the stage of cancer, histological grade, expression of TF and alphaGal epitopes in tumor tissue, patient's survival was performed. RESULTS: The level of anti-carbohydrate antibodies varied between individuals with no significant correlation between IgG immune response to the three epitopes. Lower levels of antibodies were observed at advanced stages of cancer. Neoadjuvant chemotherapy stimulated antibody production to Tn and alphaGal epitopes (increase > 50%) in about one third of patients. Immunosuppression, decrease in antibody levels, was observed only in 4.5-13.6% of cases. High levels of TF-antigen specific IgG antibody before surgery were associated with a better survival time of stage II breast cancer patients. CONCLUSION: The widely used regimens of neoadjuvant chemotherapy (such as CMF, CAF) can stimulate the immune response to tumor-associated carbohydrate epitopes in some patients. The high levels of anti-TF antibody before surgery are associated with a better survival of stage II breast cancer patients. This may indicate that the selection of immunopotentiating regimens of neoadjuvant chemotherapy might be beneficial for the host.

IgG antibodies to Lewis type 2 antigens in serum of H. pylori-infected and noninfected blood donors of different Lewis(a,b) blood-group phenotype.

Individuals of the Le(b+)/secretor phenotype revealed a stronger natural immune response to Le(x) and Le(y) epitopes irrespective of Helicobacter pylori serologic status. In contrast, H. pylori-infected Le(b-) type individuals showed a significantly higher proportion of strong responders to Le(x) antigen compared with the H. pylori-uninfected subgroup. The data suggest that the immune response to Lewis type 2 determinants is related to both the H. pylori serologic status and the Le(a,b) phenotype of the host.