Anti-ganglioside antibodies

Overview
Anti-ganglioside antibodies react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells. These antibodies show highest association with certain forms of Guillain-Barré syndrome.

Antibodies to Ganglioside subtypes
Autoantigenic gangliosides that are currently known are GD3, GM1, GQ3 and GT1.

Anti-GD3
Anti-GD3 antibodies have been found in association with specific forms of Guillain-Barre syndrome. In vivo studies of isolated anti-GM1 and GD3 antibodies indicate the antibodies can interfere with motor neuron function. Anti-GD1a antibodies were highly associated acute motor axonal neuropathy while high titers of anti-GM1 were more frequent indicating that GD1a possibly targets the axolemma and nodes of Ranvier most of the Ab+ patients had C. jejuni infections. Patients with Anti-GalNAc-GD1a antibodies were less common but had more severe disease (rapidly progressive, predominantly distal weakness).

Anti-GM1
Levels of anti-GM1 are elevated in patients with various forms of dementia. Antibodies levels correlate with more severe Guillain-Barré syndrome. In Japan, levels to GM1 were elevated in patients with prodromal diarrhea. Titers to GM1 in other diseases (rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus) was also elevated. additionally highly significant association was found with rheumatoid arthritis and peripheral neuropathies. Conflicting evidence suggests no significant elevation in motor neuron neuropathy but marginally elevated IgA in sensory neuron neuropathies. The autoimmune role of anti-GM1 is still unclear.

Anti-GQ1b
Anti-GQ1b are found in Miller-Fisher syndrome. Studies of these antibodies reveal large disruption of the Schwann cells. Anti-GQ1b IgG levels were elevated in patients with ophthalmoplegia in Gullian-Barré syndrome

Triggering agents
Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae.

Campylobacter jejuni
Antibodies to a GM1 epitope as well as to one with the GT1a or GD3 epitope were found in different strains of Campylobacter jejuni and patients with Guillain-Barré syndrome have a high occurrence of C. jejuni infection. Many studies indicate that C. jejuni may be causative for a subset of some forms of neuropathies.

Coeliac disease
Antibodies to ganglioside are found to be elevated in coeliac disease. Recent studies show that gliadin can cross-linke to gangliosides in a transglutaminase indepedent manner, indicating that gliadin specific T-cell could present these antigens to the immune system.

Immunoglobin isotypes
IgG. In multiple sclerosis, antibodies to GM1 are dominated by the IgG1, IgG3 and IgG4. Also anti-GM1 IgG has been identified in Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy. while controlled studies failed to find any significant association with these disease. IgA. IgA to gangliosides have been observe in Gullien-Barre' syndrome. IgM. IgM antibodies have been detected in early work but their significance in disease is controversial.