Immunologic mechanisms in chronic demyelinating diseases of the central and peripheral nervous system

MS and CIP are inflammatory diseases of the CNS and PNS that are characterized by focal demyelination. Both disorders are thought to involve autoimmune processes. The factors that lead to a chronic inflammatory process have not been completely defined, but the immune system is thought to play a prominent role as has been discussed in this chapter. The role of a persistent or recurrent viral exposure has not been reviewed here but may well be a contributing factor. Since chronic relapsing experimental encephalomyelitis in animal models is a T-cell-mediated disease that pathologically resembles MS, T cells are postulated to be of primary importance in human demyelinating diseases. Oligoclonal T-cell populations can be found in the CSF of MS patients, even though their antigenic specificity is not known. HLA associations (HLA Dw2 and HLA DR2 in MS and HLA Dw3 in chronic inflammatory neuropathy) might relate to the proposed immunopathogenesis, as class II antigens encoded by these loci might serve as restriction elements for T-cell recognition of an autoantigen by encephalitogenic cell populations. Humoral factors are thought to play an important role in the pathogenesis of CIP, as plasma exchange has been shown to be beneficial. Experimental work with an antimyelin glycoprotein monoclonal antibody demonstrates the in vivo demyelinating activity of antibodies as well as the importance of cellular elements in the demyelinating process. Finally, a number of immunoregulatory abnormalities have been demonstrated in MS patients that point to defects in immunoregulation, in particular in the generation of suppression. Decreases in AMLR in active MS might be of importance, as the AMLR is a reaction against self MHC determinants during which suppression is generated. Defects in suppression might allow self-reactive cells to escape regulation and cause inflammatory lesions in the nervous system.