Blood group antigen A on von Willebrand factor is more protective against ADAMTS13 cleavage than antigens B and H

Abstract

Background: ADAMTS13 specifically cleaves the peptide bond between Y1605 and M1606 within the VWF-A2 domain.

Objective: The VWF contains ABO(H) blood group antigens, which may influence the susceptibility of VWF to ADAMTS13.

Methods: Using a unique monoclonal antibody recognizing the Y1605 residue, we have developed a sandwich ELISA to analyze the generation of a VWF-DP by ADAMTS13 quantitatively.

Results: Production of VWF-DP after exposure to four different degrees of high shear stress was validated in comparison to the reduction in high-molecular-weight multimers using VWF multimer analysis. In analysis of plasma from 259 healthy individuals, plasma levels of VWF antigen (VWF:Ag) were significantly lower in blood group O than in the other groups and were significantly correlated with plasma VWF-DP levels. The ratio between VWF-DP and VWF:Ag was significantly higher in blood group O than in blood groups A and AB. The ratio in blood group B was also significantly higher than those in A and AB, but did not differ from blood group O. Finally, to examine whether ABO(H) blood group antigens contributed to VWF cleavage, 82 plasma samples were exposed to high shear stress using a cone-plate shear stress inducer. The difference in the VWF-DP/VWF:Ag ratio before and after high shear stress in blood group O was significantly greater than those in groups A and AB.

Conclusion: These results indicate that blood group antigen A on VWF was more protective against ADAMTS13 cleavage than antigens B and H.

Keywords: ABO(H) blood group; ADAMTS13; multimer analysis; shear stress; von Willebrand factor.