Affinity studies of human anti-MAG antibodies in neuropathy.

ABSTRACT

Human IgM anti-myelin associated glycoprotein (MAG) antibodies from patients with neuropathy bind to oligosaccharide determinants shared by MAG and several other glycoconjugates in peripheral nerve. The apparent affinities of human anti-MAG antibodies were determined by an ELISA system which measures free antibody concentration at equilibrium in solution. Intact MAG, which bears multiple antigenic oligosaccharides, and monovalent oligosaccharides generated by pronase digestion of MAG were used as antigen. The human antibodies bound to intact MAG with dissociation constants of between 2.5 x 10(-10) M and 2.1 x 10(-7) M, and to the monovalent oligosaccharides with up to 100-fold lower affinities. Reduction of the pentameric IgM to its monomeric counterpart reduced its affinity to intact MAG 5-fold, but its avidity for immobilized MAG was reduced 500-fold as determined by ELISA. These studies show that IgM Anti-MAG antibodies exhibit relatively low intrinsic affinities for the oligosaccharide antigen, but their affinities and avidities are significantly increased by the multivalent nature of the antibody-antigen interaction.