AFFINITY STUDIES OF HUMAN ANTI-MAG ANTIBODIES IN NEUROPATHY

Human IgM anti-myelin associated glycoprotein (MAG) antibodies from pa tients with neuropathy bind to oligosaccharide determinants shared by MAG and several other glycoconjugates in peripheral nerve. The apparen t affinities of human anti-MAG antibodies were determined by an ELISA system which measures free antibody concentration at equilibrium in so lution. Intact MAG, which bears multiple antigenic oligosaccharides, a nd monovalent oligosaccharides generated by pronase digestion of MAG w ere used as antigen. The human antibodies bound to intact MAG with dis sociation 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 affiniti es. Reduction of the pentameric IgM to its monomeric counterpart reduc ed its affinity to intact MAG 5-fold, but its avidity for immobilized MAG was reduced 500-fold as determined by ELISA. These studies show th at IgM Anti-MAG antibodies exhibit relatively low intrinsic affinities for the oligosaccharide antigen, but their affinities and avidities a re significantly increased by the multivalent nature of the antibody-a ntigen interaction.