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.
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 are found in Miller-Fisher syndrome. This presents with the classical triad of ataxia, areflexia and ophthalmoplegia. Studies of these antibodies reveal large disruption of the Schwann cells. [11] Anti-GQ1b IgG levels were elevated in patients with ophthalmoplegia in Guillain–Barré syndrome [7]
Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae. [12]
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.
Antibodies to ganglioside are found to be elevated in coeliac disease. [15] 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. [16]
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
Motor neuron disease.
[19]
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.
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.
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 are found in Miller-Fisher syndrome. This presents with the classical triad of ataxia, areflexia and ophthalmoplegia. Studies of these antibodies reveal large disruption of the Schwann cells. [11] Anti-GQ1b IgG levels were elevated in patients with ophthalmoplegia in Guillain–Barré syndrome [7]
Microbial agents include: Campylobacter jejuni and Mycoplasma pneumoniae. [12]
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.
Antibodies to ganglioside are found to be elevated in coeliac disease. [15] 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. [16]
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
Motor neuron disease.
[19]
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.