ganglioside--gd1a and Polyneuropathies

Natura non facit saltus (Latin for "nature does not make jumps") is a maxim expressing the idea that natural things and properties change gradually, in a continuum, rather than suddenly. In biomedical sciences, for taxonomic purposes, we make jumps that emphasize differences more than similarities. Among the dysimmune neuropathies, 2 disorders, characterized by the presence of antibodies to gangliosides GM1 and GD1a and a peculiar, exclusive motor involvement, have been identified: acute motor axonal neuropathy (AMAN) and multifocal motor neuropathy (MMN). However, anti-GM1 or -GD1a antibodies are also associated with acute motor and sensory axonal motor neuropathy (AMSAN). We review the results of recent clinical and experimental studies showing that AMAN and MMN are not exclusively motor. We discuss the possible explanations for the greater resistance of sensory fibers to antibody attack to finally suggest that AMAN, AMSAN, and MMN belong to a continuous spectrum with a common pathophysiological mechanism.

Topics: Antigen-Antibody Reactions; Autoantibodies; Gangliosides; Humans; Oligosaccharides; Polyneuropathies

Serum antibodies to different gangliosides have been identified in some Guillain-Barré (GBS) subtypes and variants. In the January issue of Experimental Neurology Susuki and colleagues (2012) showed that in experimental neuropathies associated with antibodies to GM1, GD1a and GD1b the common mechanism is a complement mediated dysfunction and disruption of the nodes of Ranvier which causes a pathophysiological continuum from early reversible conduction failure to axonal degeneration. These observations, correlated and integrated with electrophysiological and pathological findings in humans indicate that the GBS subtypes acute motor conduction block neuropathy, acute motor axonal neuropathy, acute motor and sensory neuropathy and acute sensory neuropathy and possibly also a chronic disorder as multifocal motor neuropathy represent a spectrum of the same immunopathologic process. Being the nodal axolemma and the paranode the focus of the nerve injury, these immune mediated neuropathies could be more properly classified as nodo-paranodopathies.

Topics: Animals; Autoantibodies; Gangliosides; Guillain-Barre Syndrome; Humans; Polyneuropathies; Sphingolipid Activator Proteins

Guillain-Barré syndrome (GBS), the most frequent cause of acute flaccid paralysis, can develop after infection by Campylobacter jejuni. The condition is often associated with serum anti-GM1 or anti-GD1a IgG antibodies. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Autoantibodies to GM1 and GD1a disrupt lipid rafts, paranodal or nodal structures, and ion channel clusters in peripheral motor nerves. Molecular mimicry exists between GM1 and GD1a gangliosides and lipo-oligosaccharides of C. jejuni isolates from GBS patients. Sensitization of rabbits with GM1 or C. jejuni lipo-oligosaccharide produces replica of GBS. These findings provide strong evidence for carbohydrate mimicry being a cause of GBS and show the role of gangliosides in peripheral nerves.

Topics: Animals; Autoimmune Diseases; Brain; Campylobacter jejuni; Cattle; Electrophysiology; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin G; Lipopolysaccharides; Mice; Polyneuropathies; Rabbits; Sialyltransferases

Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (P = .049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans.

Topics: Animals; Autoantibodies; Biomarkers; Cats; Dogs; G(M1) Ganglioside; G(M2) Ganglioside; Galactosylceramides; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Polyneuropathies