Antibody to myelin-associated glycoprotein produces central nervous system demyelination.

Antibodies to myelin-associated glycoprotein (MAG) have been implicated in certain human demyelinating diseases of the peripheral nervous system. In the present study, a monoclonal antibody to MAG with 20% guinea pig serum (GPS) was injected into mammalian optic nerves and produced in vivo demyelination associated with three ultrastructural patterns of myelin injury: (1) widened lamellae; (2) myelin vesiculation; and (3) cell-associated myelin damage. These patterns of myelin injury have been observed neuropathologically in MS and in a demyelinating peripheral neuropathy associated with plasma cell dyscrasias. Demyelination was not observed in nerves injected with anti-MAG and heated GPS or a monoclonal antibody to chick myoblasts and 20% GPS. These results establish the ability of anti-MAG to produce in vivo demyelination of mammalian CNS and indicate that a single antibody directed against a specific myelin component may initiate multiple types of myelin damage.