The Role of Antibodies Against Myelin Surface Antigens in Demyelination in Chronic EAE
Experimental allergic encephalomyelitis (EAE) is primarily mediated by T-lymphocytes. Recent studies on models of chronic EAE, however, suggest that antibodies against myelin surface antigens may play a significant additional role in the pathogenesis of demyelination.
Recently we investigated a monoclonal antibody (8-18C5), which recognizes a group of minor CNS myelin glycoproteins of molecular weights 54, 24 and 22 kilodaltons. The epitope recognized by this antibody is located at the outer surface of the myelin sheaths and on the surface of oligodendrocytes. It is highly conserved within different species, being present at identical locations in rats, guinea pigs, monkeys and man. Injection of the 8-18C5 monoclonal antibody into the cerebrospinal fluid of naive recipient animals induces primary demyelination restricted to CNS nerve fibers. Intavenous injection of 8-18C5 antibody during the course of acute EAE augments the severity of clinical disease and leads to the formation of large confluent demyelinated plaques mainly in periventricular localization. The lesions induced by this combination of acute EAE and circulating 8-18C5 antibody closely resemble those found in chronic EAE models.
Inflammatory lesions of acute EAE can be transformed into large confluent demyelinating plaques by the presence of circulating antibodies against an antigen, located at the myelin surface.
The epitope, recognized by the 8-18C5 monoclonal antibody may be an important, new target antigen in the pathogenesis of autoimmune mediated demyelination.
KeywordsPropa Alan Cholera Mycobacterium Polyneuropathy
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