title: Effector mechanisms in demyelinating neuropathies.
abstract: While the cause of the immune-mediated neuropathies (Guillain-Barr-e syndrome, GBS; CIDP; multi-focal motor neuropathy and paraproteinemic neuropathies) remains elusive considerable progress has been made in delineating the effector mechanisms that underlie myelin destruction. In GBS circulating antibodies to glycolipids possibly precipitated by an antecedent Campylobacter jejuni infection can be detected with high frequency. These antibodies may interfere with neuromuscular transmission and eventuate myelin damage by activating the complement system, providing for the generation of chemotactically active split products C3a and C5a, the opsonin C3b, and assembly of the membrane attack complex. Such antibodies may also, via binding to the Fc receptor, target macrophages to the myelin sheath. Corroborative evidence for a crucial pathogenic role of antibody-mediated complement activation is also available for the MAG-associated neuropathies. Macrophages as decisive effector cells of myelin damage may also act by releasing injurious molecules such as oxygen radicals, nitric oxide metabolites, proteases, eicosanoids and cytokines. Demyelinative as well as degenerative actions have been described for the cytokines TNF-alpha and lymphotoxin. Increased understanding of the effector mechanisms underlying demyelination may aid in developing more efficacious treatments for this group of neuropathies.
authors.affiliation: Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
authors.forename: J
authors.initials: J
authors.lastname: Zielasek
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
mesh_terms: D001323:Autoantibodies / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D003165:Complement System Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D003711:Demyelinating Diseases / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D008264:Macrophages / Q000502:physiology
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D003165:Complement System Proteins