Antiganglioside antibodies
| Autoantibody | |
|---|---|
| Anti-ganglioside | |
| Common autoantibody characteristics | |
| Triggering agent(s) |
Campylobacter jejuni (Major)
Mycoplasma pneumoniae (Minor) Coeliac Disease(Rare) |
| Isoform specific | |
| autoantibody characteristics | |
| Autoantigen Isoform |
Ganglioside D3 (GD3) |
| Affected Organ(s) | Muscle |
| Affected Cells(s) | motor nerve terminal (nodes of Ranvier) |
| Associated Disease(s) |
Guillain–Barré syndrome |
| Autoantibody class | IgA |
| Autoantigen Isoform |
Ganglioside M1 (GM1) |
| Associated Disease(s) |
prodromal diarrhea |
| Autoantibody class | IgG |
| IgG Subclass | IgG1, IgG3, IgG4 |
| Autoantigen Isoform |
Ganglioside Q1b (GQ1b) |
| Affected Cells(s) | Schwann cells |
| Associated Disease(s) |
Miller-Fisher Syndrome |
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.
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–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]
Anti-GM1
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
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]
Triggering agents
Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae.[13]
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[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.
Coeliac disease
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]
Immunoglobin isotypes
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.
References
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