Anti-ganglioside antibodies

Anti-ganglioside antibodies react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells.^[1] These antibodies show highest association with certain forms of Guillain-Barré syndrome.

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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.^[2] 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^[3] 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).^[4]

Anti-GM1

Levels of anti-GM1 are elevated in patients with various forms of dementia.^[5] Antibodies levels correlate with more severe Guillain-Barré syndrome.^[6] In Japan, levels to GM1 were elevated in patients with prodromal diarrhea.^[7] Titers to GM1 in other diseases (rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus) was also elevated.^[8] additionally highly significant association was found with rheumatoid arthritis and peripheral neuropathies.^[9] Conflicting evidence suggests no significant elevation in motor neuron neuropathy but marginally elevated IgA in sensory neuron neuropathies.^[10] 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. ^[11] Anti-GQ1b IgG levels were elevated in patients with ophthalmoplegia in Gullian-Barré syndrome^[7]

Triggering agents

Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae.^[12]

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^[13] and patients with Guillain-Barré syndrome have a high occurrence of C. jejuni infection^[14]. 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.^[15] 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.^[16]

Immunoglobin isotypes

IgG. In multiple sclerosis, antibodies to GM1 are dominated by the IgG1, IgG3 and IgG4.^[17] Also anti-GM1 IgG has been identified in Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy.^[18] while controlled studies failed to find any significant association with these disease.^[19]
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.

References