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Ganglioside complexes: new autoantibody targets in Guillain–Barré syndromes

Nature Clinical Practice Neurology volume 1, pages 2–3 (2005)Cite this article

Rarely does an experimental observation conceptually overhaul a research theme, but just such a case is illustrated by a recent analysis of immune targets for autoantibodies in the Guillain–Barré syndromes (GBS).1 Kaida et al. show that a proportion of GBS-associated autoantibodies can bind to ganglioside neoepitopes formed by pairs of gangliosides in complex, but fail to bind to either ganglioside species alone. Previous studies of the autoimmune mechanisms underlying GBS showed that antibodies against nerve glycosphingolipid (GSL) antigens are present in the acute-phase sera of patients, and have a central role in pathogenesis.2 These studies focused on identifying individually purified GSLs as targets; however, Kaida et al.'s observation forces us to reconsider our strategies for identifying new GSL antigens.

GBS is the world's leading cause of neuromuscular paralysis, affecting ∼1 in 1,000 individuals worldwide, and leaving 20% of those affected disabled or dead. GBS results from inflammation within the peripheral nervous system. The prevailing view supports a molecular mimicry hypothesis for pathogenesis, at least in a significant proportion of cases. Through a failure of immunological tolerance, autoantibodies are inadvertently formed against sugar structures on the surfaces of infectious agents (including Campylobacter jejuni), which then target identical sugar structures borne by GSLs in peripheral nerves. This process triggers a destructive cascade of inflammatory molecules, which overwhelms natural defences and results in demyelination and axonal degeneration. Current treatment is limited to plasma exchange or treatment with high-dose intravenous immunoglobulin, both of which reduce disease severity by half.

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References

  1. Kaida K et al. (2004) Ganglioside complexes as new target antigens in Guillain–Barré syndrome. Ann Neurol 56: 567–571

    Article  CAS  Google Scholar 

  2. Willison HJ and Yuki N (2002) Peripheral neuropathies and anti-glycolipid antibodies. Brain 125: 2591–2625

    Article  Google Scholar 

  3. Sandhoff K and Kolter T (2003) Biosynthesis and degradation of mammalian glycosphingolipids. Philos Trans R Soc Lond B Biol Sci 358: 847–861

    Article  CAS  Google Scholar 

  4. Yuki N et al. (2004) Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain–Barré syndrome. Proc Natl Acad Sci USA 101: 11404–11409

    Article  CAS  Google Scholar 

  5. Goodfellow JA et al. (2005) Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy. J Neurosci 25: 1620–1628

    Article  CAS  Google Scholar 

  6. Willison HJ et al. (2004) Synthetic disialylgalactose immunoadsorbents deplete anti-GQ1b antibodies from autoimmune neuropathy sera. Brain 127: 680–691

    Article  Google Scholar 

  7. Feizi T and Chai W (2004) Oligosaccharide microarrays to decipher the glyco code. Nat Rev Mol Cell Biol 5: 582–588

    Article  CAS  Google Scholar 

  8. Calarese DA et al. (2003) Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300: 2065–2071

    Article  CAS  Google Scholar 

  9. Hakomori SI (2002) Inaugural Article: The glycosynapse. Proc Natl Acad Sci USA 99: 225–232

    Article  CAS  Google Scholar 

  10. Smith AE and Helenius A (2004) How viruses enter animal cells. Science 304: 237–242

    Article  CAS  Google Scholar 

Download references

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  1. Professor of Clinical Neurology and Director of the Neuroimmunology Laboratory at the University of Glasgow and associated hospitals, Glasgow, UK

    Hugh J Willison

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  1. Hugh J Willison
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Correspondence to Hugh J Willison.

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Willison, H. Ganglioside complexes: new autoantibody targets in Guillain–Barré syndromes. Nat Rev Neurol 1, 2–3 (2005). https://doi.org/10.1038/ncpneuro0001

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