Guillain-Barré syndrome: update on immunobiology and treatment.
Growing experimental and clinical data have shed light on the pathophysiology of Guillain-Barré syndrome (GBS) and have further promoted the development of novel therapeutic strategies for the disorder. Elevated titer of antiganglioside antibodies is a characteristic of GBS. This may determine the clinical features of each case by binding to the sites where a target ganglioside antigen is localized. In experimental models of GBS and its variants, complementary inhibitory agents may exert neuroprotective efficacy by inhibiting antiganglioside antibody-mediated activation of the classical pathway. Complement-mediated disruption of the voltage-gated sodium channel cluster has been shown to be a principal cause of conduction failure in the model of acute motor axonal variants of GBS, protected by a complement inhibitor. Anti-GQ1b antibody-mediated injury at motor nerve terminals is also protected by complement inhibitors. In the future many kinds of drug candidates that inhibit activation of the complement system at various stages will be used in models of autoimmune neuropathy, in future applied to clinical trials for GBS and its variants. Complement-independent blockade of voltage-gated calcium channels or the apoptotic mechanism of neurons should also be considered. The pathogenic effect of antiganglioside antibody depends upon the local glycolipid environment in the nerve membrane as well as the antibody specificity.
Kaida
Kenichi
K
Division of Neurology, Department of Internal Medicine 3, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama-ken 359-8513, Japan. adiak901@ndmc.ac.jp
Kusunoki
Susumu
S
D003165:Complement System Proteins / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000627:therapeutic use*; D018448:Models, Immunological; D010525:Peripheral Nerves / Q000187:drug effects / Q000276:immunology*
D005732:Gangliosides; D007155:Immunologic Factors; D003165:Complement System Proteins