Antiganglioside antibodies explained

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 syndromewith 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 showthat 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.

Notes and References

  1. Gregson NA, Pytharas M, Leibowitz S . The reactivity of anti-ganglioside antiserum with isolated cerebellar cells . Biochem. Soc. Trans. . 5 . 1 . 174–5 . 1977 . 70385 . 10.1042/bst0050174.
  2. Willison HJ, O'Hanlon G, Paterson G . Mechanisms of action of anti-GM1 and anti-GQ1b ganglioside antibodies in Guillain–Barré syndrome . J. Infect. Dis. . 176 Suppl 2 . S144–9 . 1997 . 9396699 . 10.1086/513799 . etal. free .
  3. Ho TW, Willison HJ, Nachamkin I . Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain–Barré syndrome . Ann. Neurol. . 45 . 2 . 168–73 . 1999 . 9989618 . 10.1002/1531-8249(199902)45:2<168::AID-ANA6>3.0.CO;2-6 . etal.
  4. Ang CW, Yuki N, Jacobs BC . Rapidly progressive, predominantly motor Guillain–Barré syndrome with anti-GalNAc-GD1a antibodies . Neurology . 53 . 9 . 2122–7 . 1999 . 10599792 . 10.1212/wnl.53.9.2122. etal.
  5. Chapman J, Sela BA, Wertman E, Michaelson DM . Antibodies to ganglioside GM1 in patients with Alzheimer's disease . Neurosci. Lett. . 86 . 2 . 235–40 . 1988 . 3368123 . 10.1016/0304-3940(88)90577-0 .
  6. Gregson NA, Koblar S, Hughes RA . Antibodies to gangliosides in Guillain–Barré syndrome: specificity and relationship to clinical features . Q. J. Med. . 86 . 2 . 111–7 . 1993 . 8464986 .
  7. Irie S, Saito T, Kanazawa N . Relationships between anti-ganglioside antibodies and clinical characteristics of Guillain–Barré syndrome . Intern. Med. . 36 . 9 . 607–12 . 1997 . 9313102 . 10.2169/internalmedicine.36.607 . etal. free .
  8. Bansal AS, Abdul-Karim B, Malik RA . IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls . J. Clin. Pathol. . 47 . 4 . 300–2 . 1994 . 8027366 . 10.1136/jcp.47.4.300 . 501930 . etal.
  9. Salih AM, Nixon NB, Gagan RM . Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy . Br. J. Rheumatol. . 35 . 8 . 725–31 . 1996 . 8761183 . 10.1093/rheumatology/35.8.725 . etal.
  10. García Guijo C, García-Merino A, Rubio G . 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 . 1995 . 7822479 . 10.1016/0165-5728(94)00129-C .
  11. https://jamanetwork.com/journals/jamaneurology/fullarticle/2818518
  12. O'Hanlon GM, Plomp JJ, Chakrabarti M . Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal . Brain . 124 . Pt 5 . 893–906 . 2001 . 11335692 . 10.1093/brain/124.5.893 . etal. free .
  13. Sinha S, Prasad KN, Jain D, Pandey CM, Jha S, Pradhan S . 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 . 2007 . 17391394 . 10.1111/j.1469-0691.2006.01636.x. free .
  14. Yuki N, Handa S, Tai T . 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 . 1995 . 7544402 . 10.1016/0022-510X(95)00045-4 . etal.
  15. Rees JH, Gregson NA, Hughes RA . Anti-ganglioside GM1 antibodies in Guillain–Barré syndrome and their relationship to Campylobacter jejuni infection . Ann. Neurol. . 38 . 5 . 809–16 . 1995 . 7486873 . 10.1002/ana.410380516.
  16. Volta U, De Giorgio R, Granito A . Anti-ganglioside antibodies in coeliac disease with neurological disorders . Digestive and Liver Disease . 38 . 3 . 183–7 . 2006 . 16458087 . 10.1016/j.dld.2005.11.013. etal.
  17. Alaedini A, Latov N . Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside . J. Neuroimmunol. . 177 . 1–2 . 167–72 . 2006 . 16766047 . 10.1016/j.jneuroim.2006.04.022.
  18. Mathiesen T, von Holst H, Fredrikson S . Total, anti-viral, and anti-myelin IgG subclass reactivity in inflammatory diseases of the central nervous system . J. Neurol. . 236 . 4 . 238–42 . 1989 . 2760636 . 10.1007/BF00314506 . etal.
  19. McCombe PA, Wilson R, Prentice RL . Anti-ganglioside antibodies in peripheral neuropathy . Clinical and Experimental Neurology . 29 . 182–8 . 1992 . 1343861 .
  20. Willison HJ, Chancellor AM, Paterson G . Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study . J. Neurol. Sci. . 114 . 2 . 209–15 . 1993 . 8445403 . 10.1016/0022-510X(93)90300-N . etal.

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