Dual specificity of human plasma lactose-binding immunoglobulin to anomers of terminal galactose enables recognition of desialylated lipoprotein(a) and xenoantigens.

Human plasma lactose-binding immunoglobulin (LIg) isolated by affinity chromatography on lactose-Sepharose was largely IgG with significant IgA and IgM contents. LIg-mediated agglutination of desialylated human RBC was inhibited equally by the α- and β-anomers of methyl galactoside. Recognition of either the terminal α-galactose (TAG)-containing glycans of bovine thyroglobulin or the N-acetyl lactosamine (LacNAc)-terminating glycans of asialofetuin by LIg was inhibitable nearly as much by the α-galactoside melibiose as by the β-galactoside lactose. Melibiose covalently conjugated to protein and coated on polystyrene wells captured several times more LIg molecules than its lactose analogue. LIg binding to bovine thyroglobulin or rabbit RBC membrane proteins, both bearing TAG was substantially reduced by prior treatment of the proteins with α-galactosidase to remove TAG though enzyme-treated glycans contained newly exposed LacNAc moieties. Desialylated O-linked oligosaccharides, however, were no ligand for LIg. Unlike LDL, plasma lipoprotein(a) [Lp(a)] coated on polystyrene well and desialylated by neuraminidase was recognized by LIg through terminal LacNAc moieties exposed by the enzyme on its apo(a) subunit. Further, same amount of added fluorescence-labelled LIg formed significantly more immune complex with Lp(a) in high Lp(a) plasma than in low Lp(a) plasma. Results suggest (1) possibility of a role for LIg in combating non-primate molecules and cells bearing TAG moiety and (2) a mechanism for Lp(a)-mediated vascular injury as diabetes, infections and inflammations induce greater release of neuraminidase into circulation.