Glycan-binding specificities of anti-ABO(H) antibodies and lectins

ABO blood type is critically important for blood transfusion and organ transplantation. Blood group reactive glycan-binding proteins are used as reagents in clinical and research laboratories to detect the glycan epitopes that define ABO blood type. The glycan specificities of these clinically used reagents are not well defined.

We used a glycan microarray to evaluate the specificities of a series of ABO(H) glycan-binding proteins: Ulex europaeus agglutinin I (UEA-I), Helix pomatia agglutinin (HPA), Dolichos biflorus agglutinin (DBA), anti-A antibody, and anti-B antibody.

UEA-I binds many but not all H antigens and binds to some glycans that do not have the H antigen. HPA binds to terminal α-linked N-acetylgalactosamine, as found in the A antigen, but also to glycans with other terminal monosaccharides. DBA shows comparatively low binding to A antigens and binds more strongly to GM2 ganglioside sugar and Forssman antigens. Anti-A and anti-B monoclonal antibodies that are used for clinical ABO blood type determination demonstrate superior specificity compared to the lectins.

This glycan microarray data expands our understanding of the glycan specificities of commonly used ABO blood group binding reagents and indicates that caution should be used in interpretations of their binding.