Autoantibodies in guillain-barré syndrome (GBS)

Abstract

Autoantibodies contribute to the pathogenesis of Guillain-Barré syndrome (GBS) and variants such as Fisher syndrome (FS) and partly explain the pathophysiology of antibody-mediated nerve injury in GBS. The major target antigens in GBS and FS are sialic acid-containing glycolipids, gangliosides such as GM1 or GQ1b. The frequency of IgG antiglycolipid antibodies (subclass IgG1 or IgG3) is approximately 60%. The heterogeneity of ganglioside expression in the peripheral nervous system (PNS) explains the differential clinical manifestation of GBS variants. Antiganglioside antibody-mediated complement activation plays a key role in development of GBS, but some in vitro studies suggest that antibodymediated nerve dysfunction can emerge in a complement-independent manner, such as through inhibition of voltage-gated Ca2+ channel currents and changes in the integrity of lipid rafts. Pathogenic actions of antiglycolipid antibodies are regulated by the antibody avidity, which is influenced by (1) the specific distribution of target glycolipids in the PNS, (2) the glycolipid environment surrounding target antigens, (3) the amount of targeted glycolipids in specific regions, (4) the steric microstructure of sialic acids in target gangliosides, and (5) conformations of glycoepitopes. The discovery of antibodies to complexes of two gangliosides has raised the detection rate of antiglycolipid antibodies in GBS and introduced a new concept of antibody-antigen interactions through clustered carbohydrate epitopes. Peripheral nerve proteins at the nodes of Ranvier, such as neurofascin (NF) 155 and moesin, are candidates as GBS-associated antigens. Most target molecules in the demyelinating variant of GBS are unclear.