Anti-ganglioside Antibodies in Peripheral Nerve Pathology

Abstract

Anti-ganglioside antibodies are principally associated with autoimmune peripheral neuropathies. In these disorders, immune attack is inadvertently directed at peripheral nerve by autoantibodies that target glycan structures borne by glycolipids, particularly gangliosides concentrated in nerve myelin and axons. The most thoroughly studied disorder is the acute paralytic disease, Guillain-Barré syndrome (GBS) in which IgG autoantibodies against gangliosides arise following acute infections, notably Campylobacter jejuni enteritis. Additionally, chronic autoimmune neuropathies are associated with IgM antibodies directed against many glycolipids including gangliosides. This introductory chapter briefly summarizes the immunological and pathological features of these disorders, focusing on the methodological development of antibody measurement and of animal models.

Unique repertoire of anti-carbohydrate antibodies in individual human serum

“…It might be expected that ACAs toward ganglioside antigens would be relatively rare, as antibodies to self-gangliosides are associated with autoimmune diseases and autoimmune peripheral neuropathies 62 . There were, however, several individuals with both IgG and IgM ACAs to certain gangliosides.…”

The autoimmune vulnerability of the node of Ranvier

“…Anti‐ganglioside antibodies are the most commonly recognized autoimmune marker in all GBS variants: they can be found in about half of all patients in the acute phase of the disease 58 . Anti‐GM1 and anti‐GQ1b, associated with acute motor axonal neuropathy (AMAN) 59 and Miller Fisher variants, 60 respectively, are the most clinically relevant antibodies in GBS, but many other gangliosides have also been identified as antibody targets 61 . Some of these autoantibodies represent the paradigmatic example of molecular mimicry between microbial molecules, such as the lipooligosaccharides of the bacterial wall of Campylobacter jejuni , and gangliosides themselves 62,63 …”

“…58 Anti-GM1 and anti-GQ1b, associated with acute motor axonal neuropathy (AMAN) 59 and Miller Fisher variants, 60 respectively, are the most clinically relevant antibodies in GBS, but many other gangliosides have also been identified as antibody targets. 61 Some of these autoantibodies represent the paradigmatic example of molecular mimicry between microbial molecules, such as the lipooligosaccharides of the bacterial wall of Campylobacter jejuni, and gangliosides themselves. 62,63 Experimental neuropathy models using antibodies to the GM1, GD1a, and GD1b gangliosides have revealed that the common pathogenic mechanism is a complement-mediated disruption of the nodal structure that can be rapidly repaired: after acute nodal disruption, the clusters of Nav channels and paranodal components are repaired on both sides of the injured node forming two heminodes that merge in a new NoR.…”

Novel Immunological and Therapeutic Insights in Guillain-Barré Syndrome and CIDP

“…Gangliosides are sialic acid-containing glycosphingolipids present in neuronal membranes, including those of peripheral nerves, but are also minor constituents of myelin [ 111 , 112 ].…”

“…Anti-ganglioside antibodies are the most commonly recognized autoimmune marker in all GBS variants: they can be found in about half of all patients in the acute phase of GBS [ 113 ]. Anti-GM1 and anti-GQ1b, associating with AMAN [ 114 ] and Miller Fisher variants [ 115 ], are the most clinically relevant antibodies in GBS, but many other gangliosides have also been identified as antibody targets [ 111 ]. As previously described, these autoantibodies arise via microbial molecular mimicry [ 116 ].…”