title: [Search for the pathogenesis of multiple sclerosis from the bedside].
abstract: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), whereas neuromyelitis optica (NMO) is an inflammatory disease of the CNS selectively affecting the optic nerves and the spinal cord. The pathological hallmark of MS is sharply demarcated demyelinating plaque with axons relatively preserved, while in NMO both axons and myelin are involved, resulting in necrotic cavitation. The nosological position of NMO has long been a matter of debate. MS has aspects of an antigen-driven disease as well as those of a process-driven disease that is unrelated to any specific autoantigens. Research into the mechanisms of MS is rapidly progressing because of the discovery of Th17 cells producing autoimmune diseases and of NMO-IgG targeting aquaporin-4 (AQP4) on the astrocyte foot process. One hypothesis is that NMO is caused by anti-AQP4 antibodies destroying astrocyte foot processes and that it is distinct from MS. Another is that MS/NMO is caused by myelin-specific Th17 cells (or Th1 cells) and that the emergence of CNS antigen-specific autoantibodies modifies the disease. Anti-myelin antibody produces widespread demyelination whereas anti-AQP4 antibody induces astrocyte foot process injury, resulting in profuse vasogenic edema and tissue necrosis. Future research on both T cells and humoral immunity is expected to disclose the pathophysiology of MS.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies; D015551:Autoimmunity; D002490:Central Nervous System / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G; D009103:Multiple Sclerosis / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G