title: Inflammatory neuropathies.
abstract: Although not quite as well protected as in the CNS, nerve fibres in peripheral nerves are relatively protected from systemic immune responses and inflammatory reactions by the specialized endoneurial endothelial and perineurial barriers. Expression of MHC class II molecules is restricted to a few macrophage-like cells. Compared with peripheral nerve trunks, there are more of these cells and more permeable blood vessels in the dorsal root ganglia and spinal roots. These are sites of predilection for the inflammatory response in experimental allergic neuritis. This experimental disease can be induced by immunization with either of two myelin proteins, P0 and P2, and a similar but less inflammatory, more chronic demyelinating neuropathy can be induced in rabbits with the glycolipid galactocerebroside. In myelin protein induced EAN CD4+ T helper cell responses are sufficient to transfer full-blown disease but antibodies, of undefined specificity, may also play a part. In rabbit galactocerebroside neuritis, antibodies are probably more important and are directed predominantly against a haptenic group including galactose. Experimental allergic neuritis provides an accurate histological model of GBS and CIDP. A small proportion of patients with GBS and CIDP show T-cell responses to P0 and/or P2 which may mark important pathogenetic reactions. Also some patients with GBS and CIDP have antibodies to gangliosides, including for instance the most abundant peripheral nerve ganglioside LM1, which may also be important. In particular, patients with acute severe GBS and marked axonal degeneration often have IgG antibodies to GM1 and GD1b, while patients with Miller Fisher syndrome are characterized by antibodies to GQ1b. IgM antibodies to ganglioside GM1 are often found in multifocal motor neuropathy with conduction block, but are not a sensitive or specific test for that condition. Antibodies to sulphatide have recently been found in some patients with distal predominantly sensory axonal neuropathy. High titres of antibody to MAG which also react with SGPG are specific for IgM paraproteinaemic demyelinating neuropathy. Antibodies to an approximately 37kDa protein present in neuronal nuclei (Hu) are specific for paraneoplastic sensory neuronopathy usually associated with SCLC. Autoimmune responses to neural antigens have become useful diagnostically in some diseases and probably indicate important pathogenetic mechanisms. In inflammatory demyelinating neuropathy, macrophage-mediated demyelination is probably targetted by both antibody and T-cell mediated autoimmune responses. The nature of the autoantigen and the relative importance of T- versus B-cell responses are likely to vary depending on the nature of any initiating immunization and the host immunogenetic background.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Neurology, UMDS, Guy's Hospital, London, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Hughes
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001369:Axons / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D009185:Myelin Proteins / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology; D009474:Neurons / Q000276:immunology; D010525:Peripheral Nerves / Q000276:immunology; D011115:Polyneuropathies / Q000276:immunology*
chemical_list: D001324:Autoantigens; D006017:Glycolipids; D000949:Histocompatibility Antigens Class II; D009185:Myelin Proteins