Antiganglioside antibodies and their pathophysiological effects on Guillain-Barré syndrome and related disorders--a review.
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy which can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosaccharide (LOS) genes are responsible for the formation of human ganglioside-like LOS structures in infectious micro-organisms that can induce GBS. Molecular mimicry of LOSs on the surface of infectious agents and of ganglioside antigens on neural cells is thought to induce cross-reactive humoral and cellular immune responses. Patients with GBS develop antibodies against those gangliosides, resulting in autoimmune targeting of peripheral nerve sites, leading to neural damage. Heterogeneity of ganglioside expression in the peripheral nervous system (PNS) may underlie the differential clinical manifestation of the GBS variants. Recent studies demonstrate that some GBS sera react with ganglioside complexes consisting of two different gangliosides, such as GD1a and GD1b, or GM1 and GD1a, but not with each constituent ganglioside alone. The discovery of antiganglioside complex antibodies not only improves the detection rate of autoantibodies in GBS, but also provides a new concept in the antibody-antigen interaction through clustered carbohydrate epitopes. Although ganglioside mimicry is one of the possible etiological causes of GBS, unidentified factors may also contribute to the pathogenesis of GBS. While GBS is not considered a genetic disease, host factors, particularly human lymphocyte antigen type, appear to have a role in the pathogenesis of GBS following C. jejuni infection.
Kaida
Kenichi
K
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Ariga
Toshio
T
Yu
Robert K
RK
D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D008070:Lipopolysaccharides / Q000235:genetics / Q000276:immunology; D018716:Molecular Mimicry
D001323:Autoantibodies; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides