Antibodies to glycoconjugates in autoimmune neuropathies

Abstract

AbstractIn glycoconjugates, the most likely targets for autoantibodies in such autoimmune neuropathies are glycolipids, especially N‐acetylneuraminic acid‐bearing glycosphingolipids termed gangliosides. Antiganglioside antibodies are often associated with clinical phenotypes. This association depends on the diverse distribution of gangliosides in the peripheral nervous system. Complement activation is the main mechanism of antiganglioside antibody‐mediated nerve injury in Guillain–Barré syndrome. Complement‐independent mechanism, including dysfunction of ion channels, alteration of the integrity of lipid rafts and activating Fc gamma receptor‐mediated inflammation, is likely to play a role in the development of antiganglioside antibody‐mediated neuropathy. The pathogenic actions of antiganglioside antibodies are governed by their avidity, which are influenced by binding specificity of antibodies, specific localization of gangliosides in the peripheral nervous system, glycolipid environment and internalization of antibodies on nerve membranes. The discovery of antibodies to ganglioside complexes improves the detection rate of antibodies in Guillain–Barré syndrome, as well as providing a new concept in antibody–antigen interactions through clustered carbohydrate epitopes. Antibodies to glycoconjugates are infrequent in chronic inflammatory demyelinating patients, and their pathogenic roles are unclear. In multifocal motor neuropathy, Immunoglobulin M antibodies to GM1 or GM1/galactocerebroside complex are useful diagnostic markers, and are likely to induce nerve damage through complement activation. Antibodies to neutral glycolipids, such as lacytosylceramide and galactosylceramide, might play a role in the development of encephalomyeloradiculoneuropathy, a disorder involving central and peripheral nerve tissues.