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Antiganglioside antibodies

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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

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

Anti-GD3

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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

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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

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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

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

Campylobacter jejuni

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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

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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

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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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  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. doi:10.1042/bst0050174. 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. doi:10.1086/513799. 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. doi:10.1002/1531-8249(199902)45:2<168::AID-ANA6>3.0.CO;2-6. 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. doi:10.1212/wnl.53.9.2122. 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. doi:10.1016/0304-3940(88)90577-0. 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. ^ a b 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. doi:10.2169/internalmedicine.36.607. 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. doi:10.1136/jcp.47.4.300. PMC 501930. PMID 8027366.
  9. ^ Salih AM, Nixon NB, Gagan RM, et al. (1996). "Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy" (PDF). Br. J. Rheumatol. 35 (8): 725–31. doi:10.1093/rheumatology/35.8.725. 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. doi:10.1016/0165-5728(94)00129-C. PMID 7822479.
  11. ^ Lee, Sun-Uk; Kim, Hyo-Jung; Choi, Jeong-Yoon; Choi, Kwang-Dong; Kim, Ji-Soo (2024). "Expanding Clinical Spectrum of Anti-GQ1b Antibody Syndrome". JAMA Neurology. 81 (7): 762–770. doi:10.1001/jamaneurol.2024.1123. PMID 38739407.
  12. ^ 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. doi:10.1093/brain/124.5.893. PMID 11335692.
  13. ^ 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. doi:10.1111/j.1469-0691.2006.01636.x. PMID 17391394.
  14. ^ 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. doi:10.1016/0022-510X(95)00045-4. PMID 7544402.
  15. ^ 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. doi:10.1002/ana.410380516. PMID 7486873.
  16. ^ Volta U, De Giorgio R, Granito A, et al. (2006). "Anti-ganglioside antibodies in coeliac disease with neurological disorders". Digestive and Liver Disease. 38 (3): 183–7. doi:10.1016/j.dld.2005.11.013. PMID 16458087.
  17. ^ 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. doi:10.1016/j.jneuroim.2006.04.022. PMID 16766047.
  18. ^ 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. doi:10.1007/BF00314506. PMID 2760636.
  19. ^ McCombe PA, Wilson R, Prentice RL (1992). "Anti-ganglioside antibodies in peripheral neuropathy". Clinical and Experimental Neurology. 29: 182–8. PMID 1343861.
  20. ^ 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. doi:10.1016/0022-510X(93)90300-N. PMID 8445403.
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