Anti-ganglioside antibodies

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Autoantibody(s)
Anti-ganglioside
Common autoantibody characteristics
Triggering</br>agent(s) Campylobacter jejuni (Major)

Mycoplasma pneumoniae (Minor)

Coeliac Disease(Rare)

Isoform specific
autoantibody characteristics
Autoantigen
Isoform
Ganglidoside D3 (GD3)
Affected Organ(s) Muscle
Affected Cells(s) motor nerve terminal (nodes of Ranvier)
Associated</br>Disease(s) Guillain-Barré syndrome
Autoantibody class IgA
Autoantigen
Isoform
Ganglidoside M1 (GM1)
Associated</br>Disease(s) prodromal diarrhea
Autoantibody class IgG
IgG Subclass IgG1, IgG3, IgG4
Autoantigen
Isoform
Ganglidoside Q1b (GQ1b)
Affected Cells(s) Schwann cells
Associated</br>Disease(s) Miller-Fisher Syndrome

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Overview

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.

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]</br> IgA. IgA to gangliosides have been observe in Gullien-Barre' syndrome. </br> IgM. IgM antibodies have been detected in early work but their significance in disease is controversial.

References

  1. Gregson NA, Pytharas M, Leibowitz S (1977). "The reactivity of anti-ganglioside antiserum with isolated cerebellar cells". Biochem. Soc. Trans. 5 (1): 174–5. PMID 70385. 
  2. Willison HJ, O'Hanlon G, Paterson G; et al. (1997). "Mechanisms of action of anti-GM1 and anti-GQ1b ganglioside antibodies in Guillain-Barré syndrome". J. Infect. Dis. 176 Suppl 2: S144–9. PMID 9396699. 
  3. Ho TW, Willison HJ, Nachamkin I; et al. (1999). "Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barré syndrome". Ann. Neurol. 45 (2): 168–73. PMID 9989618. 
  4. Ang CW, Yuki N, Jacobs BC; et al. (1999). "Rapidly progressive, predominantly motor Guillain-Barré syndrome with anti-GalNAc-GD1a antibodies". Neurology. 53 (9): 2122–7. PMID 10599792. 
  5. Chapman J, Sela BA, Wertman E, Michaelson DM (1988). "Antibodies to ganglioside GM1 in patients with Alzheimer's disease". Neurosci. Lett. 86 (2): 235–40. PMID 3368123. 
  6. Gregson NA, Koblar S, Hughes RA (1993). "Antibodies to gangliosides in Guillain-Barré syndrome: specificity and relationship to clinical features". Q. J. Med. 86 (2): 111–7. PMID 8464986. 
  7. 7.0 7.1 Irie S, Saito T, Kanazawa N; et al. (1997). "Relationships between anti-ganglioside antibodies and clinical characteristics of Guillain-Barré syndrome". Intern. Med. 36 (9): 607–12. PMID 9313102. 
  8. Bansal AS, Abdul-Karim B, Malik RA; et al. (1994). "IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls". J. Clin. Pathol. 47 (4): 300–2. PMID 8027366. 
  9. Salih AM, Nixon NB, Gagan RM; et al. (1996). "Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy". Br. J. Rheumatol. 35 (8): 725–31. PMID 8761183. 
  10. García Guijo C, García-Merino A, Rubio G (1995). "Presence and isotype of anti-ganglioside antibodies in healthy persons, motor neuron disease, peripheral neuropathy, and other diseases of the nervous system". J. Neuroimmunol. 56 (1): 27–33. PMID 7822479. 
  11. O'Hanlon GM, Plomp JJ, Chakrabarti M; et al. (2001). "Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal". Brain. 124 (Pt 5): 893–906. PMID 11335692. 
  12. Sinha S, Prasad KN, Jain D, Pandey CM, Jha S, Pradhan S (2007). "Preceding infections and anti-ganglioside antibodies in patients with Guillain-Barré syndrome: a single centre prospective case-control study". Clin. Microbiol. Infect. 13 (3): 334–7. PMID 17391394. doi:10.1111/j.1469-0691.2006.01636.x. 
  13. Yuki N, Handa S, Tai T; et al. (1995). "Ganglioside-like epitopes of lipopolysaccharides from Campylobacter jejuni (PEN 19) in three isolates from patients with Guillain-Barré syndrome". J. Neurol. Sci. 130 (1): 112–6. PMID 7544402. 
  14. Rees JH, Gregson NA, Hughes RA (1995). "Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection". Ann. Neurol. 38 (5): 809–16. PMID 7486873. doi:10.1002/ana.410380516. 
  15. Volta U, De Giorgio R, Granito A; et al. (2006). "Anti-ganglioside antibodies in coeliac disease with neurological disorders". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 38 (3): 183–7. PMID 16458087. doi:10.1016/j.dld.2005.11.013. 
  16. Alaedini A, Latov N (2006). "Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside". J. Neuroimmunol. 177 (1-2): 167–72. PMID 16766047. doi:10.1016/j.jneuroim.2006.04.022. 
  17. Mathiesen T, von Holst H, Fredrikson S; et al. (1989). "Total, anti-viral, and anti-myelin IgG subclass reactivity in inflammatory diseases of the central nervous system". J. Neurol. 236 (4): 238–42. PMID 2760636. 
  18. McCombe PA, Wilson R, Prentice RL (1992). "Anti-ganglioside antibodies in peripheral neuropathy". Clinical and experimental neurology. 29: 182–8. PMID 1343861. 
  19. Willison HJ, Chancellor AM, Paterson G; et al. (1993). "Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study". J. Neurol. Sci. 114 (2): 209–15. PMID 8445403. 





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