Antiganglioside antibodies

Antiganglioside antibodies that 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.

Autoantigenic gangliosides that are currently known are GD3, GM1, GQ3 and GT1.

Anti-GD3 antibodies have been found in association with specific forms of Guillain–Barré 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]

Levels of anti-GM1 antibodies are elevated in patients with various forms of dementia.^[5] Antibodies levels correlate with more severe Guillain–Barré syndrome.^[6] Levels of anti-GM1 antibodies are especially 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. Multifocal motor neuropathy (MMN) with conduction block is closely related to CIDP (chronic inflammatory demyelinating polyneuropathy). Anti-GM1 antibodies are positive in around 80% of cases. MMN will present with asymmetrical motor neuropathy where reflexes are usually preserved (or slightly increased), affecting upper limb more than lower limb. MMN is potentially treatable with immunomodulation.

Anti-GQ1b were typically described in Miller-Fisher syndrome. This presents with the classical triad of ataxia, areflexia and ophthalmoplegia. The clinical spectrum of disorders associated with anti-GQ1b now is also recognized to include, Bickerstaff brainstem encephalitis, Guillain-Barré syndrome with ophthalmoplegia, and acute ophthalmoplegia without ataxia.^[11] Studies of these antibodies reveal large disruption of the Schwann cells.^{[12] [7]}

Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae.^[13]

Antibodies to a GM1 epitope as well as to one with the GT1a or GD3 epitope were found in different strains of Campylobacter jejuni^[14] and patients with Guillain–Barré syndrome have a high occurrence of C. jejuni infection.^[15] Many studies indicate that C. jejuni may be causative for a subset of some forms of neuropathies.

Antibodies to ganglioside are found to be elevated in coeliac disease.^[16] Recent studies show that gliadin can cross-link to gangliosides in a transglutaminase independent manner, indicating that gliadin specific T-cell could present these antigens to the immune system.^[17]

IgG. In multiple sclerosis, antibodies to GM1 are dominated by the IgG1, IgG3 and IgG4.^[18] Also anti-GM1 IgG has been identified in Guillain–Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy.^[19] while controlled studies failed to find any significant association with Motor neuron disease.^[20]
IgA. IgA to gangliosides have been observed in Guillain–Barré syndrome.
IgM. IgM antibodies have been detected in early work, but their significance in disease is controversial.