Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: A case for antigen-specific antibody mediation

Neuropathological and ultrastructural features of central nervous system de myelination were compared in marmoset experimental autoimmune encephalomyel itis (EAE) induced with myelin/oligodendrocyte glycoprotein (MOG), and in 3 cases of multiple sclerosis (MS) displaying recent lesions. At the edges o f EAE and MS lesions, a zone of myelin vacuolation was common, whereas in t he lesion proper, myelin sheaths were consistently transformed into vesicul ated membranous networks. These networks became dissociated from axons by c ell processes from macrophages. Oligodendrocytes were remarkably spared and evidence of myelin repair was present but not prominent. Axonal pathology was more common in the MS material than in marmoset EAE. Immunocytochemistr y, using gold-labeled encephalitogenic peptides of MOG and silver enhanceme nt to detect MOG autoantibodies, revealed the presence of MOG-specitic auto antibodies over vesiculated myelin networks. Gold-labeled antibody to IgG a lso gave a positive reaction. Gold-labeled peptide of myelin basic protein did not react with MOG/EAE tissue, but the same conjugate gave positive sta ining in MS land in marmoset EAE induced by whole white matter), perhaps in dicating broader spectrum immunoreactivity or sensitization to myelin antig ens, Thus, vesicular disruption of myelin was a constant feature in these e volving, highly active lesions in primate EAE and MS and appeared causally related to the deposition of antigen-specific autoantibodies.