The TF, Tn, and SiaTn glycotopes are frequently expressed in cancer-associated mucins. Antibodies to these glycotopes were found in human serum. A set of polyacrylamide (PAA)--based glycoconjugates was applied to the direct and competitive enzyme-linked immunosorbent assays (ELISA) to characterize the specificity of serum IgG antibodies. The anti-TF, -Tn and -SiaTn IgG were affinity purified from serum of cancer patients and characterized using PAA-conjugates and free saccharides. The anti-TF and -Tn antibodies were shown to be specific. The anti-TF IgG bound both Galbeta1-3GalNAcalpha- and Galbeta1-3GalNAcbeta-PAA, the latter was three-four times more effective inhibitor of antibody binding. The anti-Tn IgG reacted only with GalNAcalpha-PAA. The anti-SiaTn IgG cross-reacted with Tn-PAA but SiaTn-PAA was five-six times more effective inhibitor in a competitive assay. The IC50 values for PAA-conjugates with the corresponding antibodies typically ranged from 2 to 5 x 10(-8) M. The antibodies display a low specificity to mucin-type glycoconjugates in comparison with PAA-conjugates as was shown for mucins isolated from human malignant tumor tissues, ovine submaxillary mucin (OSM) and asialo-OSM. The unusual IgG-antibody specificity to GalNAcbeta and GalNAcbeta1-3GalNAcbeta ligands was found in human serum.
Objective: To evaluate the relation of the level of serum anti-TF, -Tn and -αGal carbohydrate antibodies to survival in gastrointestinal cancer patients.Methods: The level of anti-TF (Thomsen-Friedenreich antigen), -Tn and -αGal IgG was analysed in the serum of patients with gastric (n = 83) and colorectal (n = 51) cancers in the long-term follow-up, using ELISA with polyacrylamide glycoconjugates. To evaluate overall survival and the risk of death, the Kaplan-Meier method and the Cox proportional hazards model were used in the univariate analysis of patients groups.Results: A significantly better survival was observed: (1) in patients with an increased level of anti-TF antibodies (all, stage III, T2-4, N1-2 and G3; P = 0.004-0.038, HR = 0.16-0.46); and (2) in patients with an increased level of anti-Tn antibodies (G1-2 tumors; P = 0.034-0.042, HR = 0.34-0.47). A significantly worse survival was observed in gastrointestinal, gastric and colorectal groups with an increased level of serum anti-αGal antibodies. This association depended on the patho-morphology of tumors (all, stages I-II, III, T2-4, N0, N1-2 and G1-2; P = 0.006-0.048, HR = 1.99-2.33). In the combined assessment of the anti-TF and -αGal antibodies level of the whole gastrointestinal group (n = 53), P = 0.002, HR = 0.25, 95% CI 0.094-0.655. In the follow-up, the survival time was shorter in patients whose level of anti-αGal antibodies rose (P = 0.009-0.040, HR = 2.18-4.27). The level of anti-TF antibodies inversely correlated with neutrophil/lymphocyte ratio (NLR, r = - 0.401, P = 0.004, n = 49). Patients with a higher level of anti-αGal antibodies and NLR values demonstrated a significantly worse survival (P = 0.009, HR = 2.98, n = 48).Conclusions: The preoperative levels of anti-TF, -Tn and -αGal antibodies and their dynamics are of prognostic significance. The method for the determination of circulating anti-carbohydrate antibodies may be a useful supplement in clinical outcome assessment.
AIM:To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic αGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages Ⅰ-Ⅳ without distant metastases were subjected to followup. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and αGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cutoff value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (χ 2 = 3.89, all patients; χ 2 = 5.34, patients without regional lymph node metastases; P < 0. No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stageand morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.
Changes in the glycosylation in cancer may lead to an aberrant expression of A, B incompatible or xenogeneic blood group related antigens. To characterize the specificity of IgG antibodies to A, B, and related glycans in sera of gastrointestinal cancer patients, serum probes and affinity-isolated antibodies were analyzed in the indirect and competitive ELISA using a set of homogenous polyacrylamide (PAA) glycoconjugates. Monoreactive antibodies recognizing A(di) (I) and cross-reactive antibodies to A(di)/B(di)/B(tri) (II) or A(di)/A(tri)/Fs(di)/Core5 (III) were affinity-isolated on A(di)-PAA-Sepharose. The population I showed a higher affinity to A(di)-PAA than cross-reactive antibodies. The antibodies II were more specific to B(di) and may belong to the core alpha-Gal reactive antibodies but are also capable of recognizing A(di). The antibodies III were more specific to A(tri); they agglutinated A-erythrocytes and belong to anti-A isoantibodies reactive to xenogeneic oligosaccharides. The purified antibody samples were non- or faintly reactive to Tn. The IC(50) values of PAA glycoconjugates ranged from 6 × 10(-8) to 7 × 10(-6) M. No or weak binding of antibodies to the unrelated antigens used in the detection of polyreactivity (ferritin, casein, and DNA) was observed.
Background: The serum levels of IgG antibodies reactive to glycoconjugates (TF, Tn and αGal) were found to be associated with prognosis of gastrointestinal cancer patients. Aim: To study the relation between the levels of serum antibodies to TF-pAA, Tn-PAA and αGal-PAA polyacrylamide-based glycoconjugates and survival in breast cancer. Materials and Methods: The preoperative level of IgG antibodies was analysed in the serum of patients (n = 59) using ELISA with polyacrylamide-glycoconjugates namely, TF-pAA (amide-type), and ethanolamide-conjugates Tn-PAA and αGal-PAA. Survival rate and hazard ratio (HR) were assessed by the Kaplan — Meier method and Cox univariate analysis in different pathomorphological groups. Results: Significantly better survival was observed in patients with an increased level of anti-TF-pAA antibodies both for all patients in total and groups in stages II–III; N1–2 and G3 (p = 0.008–0.021, HR = 0.18–0.23, mean survival time in months 164–186 vs 69–121). A trend to worse survival was observed in increased level of anti-Tn IgG (stages II–III) and anti-αGal IgG (G3): p = 0.075, HR = 2.49 and p = 0.066, HR = 3.27, respectively. Conclusion: The method for the determination of circulating anti-TF-pAA IgG may be a useful supplement in long-term prognostic assessment of patients with breast cancer.
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