The Thomsen-Friedenreich Antigen and αGal-specific Human IgG Glycoforms: Concanavalin A Reactivity and Relation to Survival of Cancer Patients

Abstract

Glycan structures of IgG strongly influence the affinity for Fcγ receptors and antibody effector functions. However, no particular attention has been paid yet to the glycosylation of tumor antigen-specific IgG. The objectives of this study were (i) to investigate the concanavalin A lectin (ConA) reactivity of human anti-Thomsen-Friedenreich (TF) and anti-αGal specific IgG in gastric cancer patients and healthy controls and (ii) to evaluate whether the ConA-reactivity of anti-TF and anti-αGal specific IgG is associated with the survival rate of patients with cancer. Total IgG was purified from the sera of patients with gastric cancer and healthy blood donors. The anti-TF and anti-αGal glycotope specific IgG were detected with ELISA using synthetic saccharide-polyacrylamide conjugates as antigen. In parallel plate, the ConA reactivity of the anti-TF or anti-αGal IgG was determined and the ConA index was calculated. Results show that serum anti-TF specific IgG antibodies of patients with cancer contain significantly higher content of ConA positive IgG glycoform compared to IgG of controls. No correlation between the ConA reactivity of anti-TF IgG and anti-αGal IgG was observed. High level of anti-TF IgG ConA reactivity was associated with a significantly lower survival rate of patients with gastric cancer.

Keywords:

• Tumor immunity
• IgG glycosylation
• Thomsen-Friedenreich antigen
• Alpha-Gal
• Concanavalin A
• Cancer patients survival
• Lectin-ELISA

ACKNOWLEDGEMENTS

We thank Kate Rittenhouse-Olson (The University of Buffalo, Buffalo, N.Y.) for providing the mouse monoclonal JAA-F11 antibody. This work was supported by the Estonian Science Foundation, Grants #7317 and #6726.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.