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 syndrome
with ophthalmoplegia, and acute ophthalmoplegia without ataxia.[11] Studies of these antibodies reveal large disruption of the Schwann cells.[12][7]
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 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
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
^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. PMID70385.
^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. PMID10599792.
^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. PMID3368123.
^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. PMID8464986.
^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. PMID7822479.
^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. PMID7544402.
^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. PMID7486873.
^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. PMID16458087.
^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. PMID16766047.
^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. PMID2760636.
^McCombe PA, Wilson R, Prentice RL (1992). "Anti-ganglioside antibodies in peripheral neuropathy". Clinical and Experimental Neurology. 29: 182–8. PMID1343861.
^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. PMID8445403.