Autoimmune Responses to the Myelin Oligodendrocyte Glycoprotein (MOG) in the Pathogenesis of Inflammatory Demyelinating Diseases of the Central Nervous System
A T cell mediated autoimmune response is believed to trigger the characteristic inflammatory demyelinating pathology of multiple sclerosis (MS)1 . However the immune effector mechanisms responsible for the selective loss of myelin in MS have still to be defined. Several authors have suggested that demyelination in MS is simply a consequence of the local inflammatory response in the CNS, “bystander demyelination”. In vitro studies demonstrating that oligodendrocytes and myelin are highly susceptible to damage by a wide variety agents released by monocytes and T cells during an inflammatory response 2,3. However, ultrastructural and immunocytochemical studies indicate that primary demyelination in MS may be mediated by a specific humoral response directed against the myelin membrane. Electron microscopy reveals that macrophages attack, phagocytose and degrade apparently normal myelin in MS 4, introducing processes between myelin lamellae and actively stripping sheets of membrane from the myelin sheath, which is then phagocytosed by a process resembling receptor mediated endocytosis. Interestingly the phagocytosis of myelin is closely associated with the capping of IgG on the macrophage surface suggesting that a specific receptor/ligand interaction is involved in this process5. The ligands involved in this interaction are unknown, but possible candidates are immunoglobulin or complement activation products (C3bi) deposited on the myelin surface. In MS there is certainly ample indirect evidence for the activation of complement on myelin surface, in particular, the intrathecal consumption of complement 6 and the presence of myelin membrane fragments coated with terminal complement complexes the cerebrospinal fluid 7. The deposition of terminal complement components and immunoglobulins can also be demonstrated in MS lesions8,9. However, as yet no myelin-specific autoantibody response has been identified that can account for the observed intrathecal activation of complement in MS.
KeywordsMultiple Sclerosis Myelin Basic Protein Autoimmune Response Experimental Allergic Encephalomyelitis Myelin Oligodendrocyte Glycoprotein
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