Antibodies to glycoconjugates in autoimmune neuropathies

Abstract

In 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-Barr e 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-Barr e syndrome, as well as providing a new concept in antibodyantigen 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.

Genome expression profiling predicts the molecular mechanism of peripheral myelination

“…FCGR has previously been identified in SCs, which may aid in the regulation of the immune response ( 35 ). A recent study reported that FCGR had a potential role in axonal injury through the mediation of inflammation ( 36 ). RAC2 has been previously identified as stimulating AKT activation in primary mast cells ( 37 ).…”

Experimental approach in research of Guillain–Barré syndrome: A range of pathogeneses mediated by molecular mimicry

“…Briefly, in sera from patients with C . jejuni ‐associated GBS, levels of immunoglobulin G (IgG) autoantibodies against various gangliosides (GM1, GM1b, GD1a and GalNAc‐GD1a) are transiently increased during the acute phase of the illness . Mass spectrometry analyses showed that sugar sequences identical to those of GM1 and GD1a are expressed on the lipo‐oligosaccharide (LOS) of the C .…”

“…Briefly, in sera from patients with C. jejuni-associated GBS, levels of immunoglobulin G (IgG) autoantibodies against various gangliosides (GM1, GM1b, GD1a and GalNAc-GD1a) are transiently increased during the acute phase of the illness. 6 Mass spectrometry analyses showed that sugar sequences identical to those of GM1 and GD1a are expressed on the lipo-oligosaccharide (LOS) of the C. jejuni strains isolated from GBS patients. [28][29][30] On sensitization with GM1-like C. jejuni LOS isolated from a GBS patient, rabbits developed acute motor axonal neuropathy with anti-GM1 IgG antibodies that resembled with human C. jejuni-associated GBS.…”

“…These obstacles could be addressed by the use of Guillain–Barré syndrome (GBS), an acute motor‐dominant neuropathy that can be triggered by various antecedent infections, as a model disease . Several lines of evidence show a pathogenic role for autoantibodies against various glycolipids, especially gangliosides, which are sialic acid‐bearing glycosphingolipids concentrated in the outer leaflet of neuronal cell membranes . The finding that most GBS patients experience preceding infectious symptoms shortly before onset of neurological symptoms, and that a spectrum of antecedent infections has been partially determined, provides the opportunity to isolate causal microorganisms from GBS patients.…”

“…4,5 Several lines of evidence show a pathogenic role for autoantibodies against various glycolipids, especially gangliosides, which are sialic acid-bearing glycosphingolipids concentrated in the outer leaflet of neuronal cell membranes. 6 The finding that most GBS patients experience preceding infectious symptoms shortly before onset of neurological symptoms, 7 and that a spectrum of antecedent infections has been partially determined, 8 provides the opportunity to isolate causal microorganisms from GBS patients. The ability to use such clinical isolates of GBS-causative microorganisms would be advantageous for the study of whether mimicry occurs in GBS.…”