Anti-ganglioside antibodies

AutoAbBox
Autoantigen = ganglioside
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SharedInfo = Yes
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SI_Trigger = "Campylobacter jejuni" (Major)

"Mycoplasma pneumoniae" (Minor)

Coeliac Disease(Rare)
Isoform1 = Ganglidoside D3 (GD3)
I1_Gene =
I1_Organ = Muscle
I1_Tissue =
I1_Cell = motor nerve terminal (nodes of Ranvier)
I1_Also =
I1_Disease = Guillain-Barré syndrome
I1_Class = IgA
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Isoform2 = Ganglidoside M1 (GM1)
I2_Gene =
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I2_Disease = prodromal diarrhea
I2_Class = IgG
I2_IgGSubclass = IgG1, IgG3, IgG4
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Isoform3 = Ganglidoside Q1b (GQ1b)
I3_Gene =
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I3_Tissue =
I3_Cell = Schwann cells
I3_Also =
I3_Disease = Miller-Fisher Syndrome
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Anti-ganglioside antibodies react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells.cite journal | author = Gregson NA, Pytharas M, Leibowitz S | title = The reactivity of anti-ganglioside antiserum with isolated cerebellar cells | journal = Biochem. Soc. Trans. | volume = 5 | issue = 1 | pages = 174–5 | year = 1977 | pmid = 70385 | doi = ] 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.cite journal | author = Willison HJ, O'Hanlon G, Paterson G, "et al" | title = Mechanisms of action of anti-GM1 and anti-GQ1b ganglioside antibodies in Guillain-Barré syndrome | journal = J. Infect. Dis. | volume = 176 Suppl 2 | issue = | pages = S144–9 | year = 1997 | pmid = 9396699 | doi = ] 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 Ranviercite journal | author = Ho TW, Willison HJ, Nachamkin I, "et al" | title = Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barré syndrome | journal = Ann. Neurol. | volume = 45 | issue = 2 | pages = 168–73 | year = 1999 | pmid = 9989618 | doi = ] 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).cite journal | author = Ang CW, Yuki N, Jacobs BC, "et al" | title = Rapidly progressive, predominantly motor Guillain-Barré syndrome with anti-GalNAc-GD1a antibodies | journal = Neurology | volume = 53 | issue = 9 | pages = 2122–7 | year = 1999 | pmid = 10599792 | doi = ]

Anti-GM1

Levels of anti-GM1 are elevated in patients with various forms of dementia.cite journal | author = Chapman J, Sela BA, Wertman E, Michaelson DM | title = Antibodies to ganglioside GM1 in patients with Alzheimer's disease | journal = Neurosci. Lett. | volume = 86 | issue = 2 | pages = 235–40 | year = 1988 | pmid = 3368123 | doi = ] Antibodies levels correlate with more severe Guillain-Barré syndrome.cite journal | author = Gregson NA, Koblar S, Hughes RA | title = Antibodies to gangliosides in Guillain-Barré syndrome: specificity and relationship to clinical features | journal = Q. J. Med. | volume = 86 | issue = 2 | pages = 111–7 | year = 1993 | pmid = 8464986 | doi = ] In Japan, levels to GM1 were elevated in patients with prodromal diarrhea.cite journal | author = Irie S, Saito T, Kanazawa N, "et al" | title = Relationships between anti-ganglioside antibodies and clinical characteristics of Guillain-Barré syndrome | journal = Intern. Med. | volume = 36 | issue = 9 | pages = 607–12 | year = 1997 | pmid = 9313102 | doi = ] Titers to GM1 in other diseases (rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus) was also elevated.cite journal | author = Bansal AS, Abdul-Karim B, Malik RA, "et al" | title = IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls | journal = J. Clin. Pathol. | volume = 47 | issue = 4 | pages = 300–2 | year = 1994 | pmid = 8027366 | doi = ] additionally highly significant association was found with rheumatoid arthritis and peripheral neuropathies.cite journal | author = Salih AM, Nixon NB, Gagan RM, "et al" | title = Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy | journal = Br. J. Rheumatol. | volume = 35 | issue = 8 | pages = 725–31 | year = 1996 | pmid = 8761183 | doi = ] Conflicting evidence suggests no significant elevation in motor neuron neuropathy but marginally elevated IgA in sensory neuron neuropathies.cite journal | author = García Guijo C, García-Merino A, Rubio G | title = Presence and isotype of anti-ganglioside antibodies in healthy persons, motor neuron disease, peripheral neuropathy, and other diseases of the nervous system | journal = J. Neuroimmunol. | volume = 56 | issue = 1 | pages = 27–33 | year = 1995 | pmid = 7822479 | doi = ] 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. cite journal | author = O'Hanlon GM, Plomp JJ, Chakrabarti M, "et al" | title = Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal | journal = Brain | volume = 124 | issue = Pt 5 | pages = 893–906 | year = 2001 | pmid = 11335692 | doi = ] Anti-GQ1b IgG levels were elevated in patients with ophthalmoplegia in Gullian-Barré syndrome

Triggering agents

Microbial agents include: "Campylobacter jejuni" and "Mycoplasma pneumoniae".cite journal | author = Sinha S, Prasad KN, Jain D, Pandey CM, Jha S, Pradhan S | title = Preceding infections and anti-ganglioside antibodies in patients with Guillain-Barré syndrome: a single centre prospective case-control study | journal = Clin. Microbiol. Infect. | volume = 13 | issue = 3 | pages = 334–7 | year = 2007 | pmid = 17391394 | doi = 10.1111/j.1469-0691.2006.01636.x]

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"cite journal | author = Yuki N, Handa S, Tai T, "et al" | title = Ganglioside-like epitopes of lipopolysaccharides from Campylobacter jejuni (PEN 19) in three isolates from patients with Guillain-Barré syndrome | journal = J. Neurol. Sci. | volume = 130 | issue = 1 | pages = 112–6 | year = 1995 | pmid = 7544402 | doi = ] and patients with Guillain-Barré syndrome have a high occurrence of "C. jejuni" infectioncite journal | author = Rees JH, Gregson NA, Hughes RA | title = Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection | journal = Ann. Neurol. | volume = 38 | issue = 5 | pages = 809–16 | year = 1995 | pmid = 7486873 | doi = 10.1002/ana.410380516] . 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.cite journal | author = Volta U, De Giorgio R, Granito A, "et al" | title = Anti-ganglioside antibodies in coeliac disease with neurological disorders | journal = Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | volume = 38 | issue = 3 | pages = 183–7 | year = 2006 | pmid = 16458087 | doi = 10.1016/j.dld.2005.11.013] Recent studies showthat 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.cite journal | author = Alaedini A, Latov N | title = Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside | journal = J. Neuroimmunol. | volume = 177 | issue = 1-2 | pages = 167–72 | year = 2006 | pmid = 16766047 | doi = 10.1016/j.jneuroim.2006.04.022]

Immunoglobin isotypes

IgG. In multiple sclerosis, antibodies to GM1 are dominated by the IgG1, IgG3 and IgG4.cite journal | author = Mathiesen T, von Holst H, Fredrikson S, "et al" | title = Total, anti-viral, and anti-myelin IgG subclass reactivity in inflammatory diseases of the central nervous system | journal = J. Neurol. | volume = 236 | issue = 4 | pages = 238–42 | year = 1989 | pmid = 2760636 | doi = ] Also anti-GM1 IgG has been identified in Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy.cite journal | author = McCombe PA, Wilson R, Prentice RL | title = Anti-ganglioside antibodies in peripheral neuropathy | journal = Clinical and experimental neurology | volume = 29 | issue = | pages = 182–8 | year = 1992 | pmid = 1343861 | doi = ] while controlled studies failed to find any significant association with these disease.cite journal | author = Willison HJ, Chancellor AM, Paterson G, "et al" | title = Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study | journal = J. Neurol. Sci. | volume = 114 | issue = 2 | pages = 209–15 | year = 1993 | pmid = 8445403 | doi = ]
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