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Human Gangliosides and Bacterial Lipo-oligosaccharides in the Development of Autoimmune Neuropathies

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Functional Glycomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 600))

Abstract

Guillain–Barré syndrome (GBS), the most frequent cause of acute flaccid paralysis, can develop after infection by Campylobacter jejuni. The condition is often associated with serum anti-GM1 or anti-GD1a IgG antibodies. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Autoantibodies to GM1 and GD1a disrupt lipid rafts, paranodal or nodal structures, and ion channel clusters in peripheral motor nerves. Molecular mimicry exists between GM1 and GD1a gangliosides and lipo-oligosaccharides of C. jejuni isolates from GBS patients. Sensitization of rabbits with GM1 or C. jejuni lipo-oligosaccharide produces replica of GBS. These findings provide strong evidence for carbohydrate mimicry being a cause of GBS and show the role of gangliosides in peripheral nerves.

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References

  1. Hafer-Macko, C., Hsieh, S.-T., Li, C. Y., Ho, T. W., Sheikh, K., Cornblath, D. R., McKhann, G. M., Asbury, A. K., and Griffin, J. W. (1996) Acute motor axonal neuropathy: an antibody-mediated attack on axolemma. Ann. Neurol. 40, 635–644.

    Article  CAS  PubMed  Google Scholar 

  2. Hafer-Macko, C. E., Sheikh, K. A., Li, C. Y., Ho, T. W., Cornblath, D. R., McKhann, G. M., Asbury, A. K., and Griffin, J. W. (1996) Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann. Neurol. 39, 625–635.

    Article  CAS  PubMed  Google Scholar 

  3. Ang, C. W., Jacobs, B. C., and Laman, J. D. (2004) The Guillain-Barré syndrome: a true case of molecular mimicry. Trends Immunol. 25, 61–66.

    Article  CAS  PubMed  Google Scholar 

  4. Jacobs, B. C., Rothbarth, P. H., van der Meché, F. G. A., Herbrink, P., Schmitz, P. I. M., de Klerk, M. A., and van Doorn, P. A. (1998) The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study. Neurology 51, 1110–1115.

    CAS  PubMed  Google Scholar 

  5. Rees, J. H., Soudain, S. E., Gregson, N. A., and Hughes, R. A. C. (1995) Campylobacter jejuni infection and Guillain-Barré syndrome. N Engl. J. Med. 333, 1374–1379.

    Article  CAS  PubMed  Google Scholar 

  6. Kuwabara, S., Ogawara, K., Misawa, S., Koga, M., Mori, M., Hiraga, A., Kanesaka, T., Hattori, T., and Yuki, N. (2004) Does Campylobacter jejuni infection elicit “demyelinating" Guillain-Barré syndrome? Neurology 63, 529–533.

    CAS  PubMed  Google Scholar 

  7. Yuki, N., Yoshino, H., Sato, S., and Miyatake, T. (1990) Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis. Neurology 40, 1900–1902.

    CAS  PubMed  Google Scholar 

  8. Ho, T. W., Willison, H. J., Nachamkin, I., Li, C. Y., Veitch, J., Ung, H., Wang, G. R., Liu, R. C., Cornblath, D. R., Asbury, A. K., Griffin, J. W., and McKhann, G. M. (1999) Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barré syndrome. Ann. Neurol. 45, 168–173.

    Article  CAS  PubMed  Google Scholar 

  9. Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Motoneuron-disease-like disorder after ganglioside therapy. Lancet 337, 1109–1110.

    Article  CAS  PubMed  Google Scholar 

  10. Illa, I., Ortiz, N., Gallard, E., Juarez, C., Grau, J. M., and Dalakas, M. C. (1995) Acute axonal Guillain-Barré syndrome with IgG antibodies against motor axons following parenteral gangliosides. Ann. Neurol. 38, 218–224.

    Article  CAS  PubMed  Google Scholar 

  11. Yuki, N., Taki, T., Inagaki, F., Kasama, T., Takahashi, M., Saito, K., Handa, S., and Miyatake, T. (1993) A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure. J. Exp. Med. 178, 1771–1775.

    Article  CAS  PubMed  Google Scholar 

  12. Matsumoto, Y., Yuki, N., van Kaer, L., Furukawa, K., Hirata, K., and Sugita, M. (2008) Guillain-Barré syndrome-associated IgG responses to gangliosides are generated independently of CD1 function in mice. J. Immunol. 180, 39–43.

    CAS  PubMed  Google Scholar 

  13. Koga, M., Gilbert, M., Takahashi, M., Li, J., Koike, S., Hirata, K., and Yuki, N. (2006) Comprehensive analysis of bacterial risk factors for the development of Guillain-Barré syndrome after Campylobacter jejuni enteritis. J. Infect. Dis. 193, 547–555.

    Article  CAS  PubMed  Google Scholar 

  14. Yuki, N., Yamada, M., Koga, M., Odaka, M., Susuki, K., Tagawa, Y., Ueda, S., Kasama, T., Ohnishi, A., Hayashi, S., Takahashi, H., Kamijo, M., and Hirata, K. (2001) Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganglioside. Ann. Neurol. 49, 712–720.

    Article  CAS  PubMed  Google Scholar 

  15. Comín, R., Yuki, N., Lopez, P. H., and Nores, G. A. (2006) High affinity of anti-GM1 antibodies is associated with disease onset in experimental neuropathy. J. Neurosci. Res. 84, 1085–1090.

    Article  PubMed  Google Scholar 

  16. Susuki, K., Nishimoto, Y., Yamada, M., Baba, M., Ueda, S., Hirata, K., and Yuki, N. (2003) Acute motor axonal neuropathy rabbit model: immune attack on nerve root axons. Ann. Neurol. 54, 383–388.

    Article  PubMed  Google Scholar 

  17. Yuki, N., Susuki, K., Koga, M., Nishimoto, Y., Odaka, M., Hirata, K., Taguchi, K., Miyatake, T., Furukawa, K., Kobata, T., and Yamada, M. (2004) Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barré syndrome. Proc. Natl. Acad. Sci. U. S. A. 101, 11404–11409.

    Article  CAS  PubMed  Google Scholar 

  18. Yuki, N., Ichihashi, Y., and Taki, T. (1995) Subclass of IgG antibody to GM1 epitope-bearing lipopolysaccharide of Campylobacter jejuni in patients with Guillain-Barré syndrome. J. Neuroimmunol. 60, 161–164.

    Article  CAS  PubMed  Google Scholar 

  19. Susuki, K., Baba, H., Tohyama, K., Kanai, K., Kuwabara, S., Hirata, K., Furukawa, K., Furukawa, K., Rasband, M. N., and Yuki, N. (2007) Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Glia 55, 746–757.

    Article  PubMed  Google Scholar 

  20. Hirota, N., Kaji, R., Bostock, H., Shindo, K., Kawasaki, T., Mizutani, K., Oka, N., Kohara, N., Saida, T., and Kimura, J. (1997) The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons. Brain 120, 2159–2169.

    Article  PubMed  Google Scholar 

  21. Takigawa, T., Yasuda, H., Kikkawa, R., Shigeta, Y., Saida, T., and Kitasato, H. (1995) Antibodies against GM1 ganglioside affect K+ and Na+ currents in isolated rat myelinated nerve fibers. Ann. Neurol. 37, 436–442.

    Article  CAS  PubMed  Google Scholar 

  22. Susuki, K., Rasband, M. N., Tohyama, K., Koibuchi, K., Okamoto, S., Funakoshi, K., Hirata, K., Baba, H., and Yuki, N. (2007) Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers. J. Neurosci. 27, 3956–3967.

    Article  CAS  PubMed  Google Scholar 

  23. Waxman, S. G. (1995) Sodium channel blockade by antibodies: a new mechanism of neurological disease? Ann. Neurol. 37, 421–423.

    Article  CAS  PubMed  Google Scholar 

  24. Halstead, S. K., Humphreys, P. D., Goodfellow, J. A., Wagner, E. R., Smith, R. A., and Willison, H. J. (2005) Complement inhibition abrogates nerve terminal injury in Miller Fisher syndrome. Ann. Neurol. 58, 203–210.

    Article  CAS  PubMed  Google Scholar 

  25. Halstead, S. K., Zitman, F. M., Humphreys, P. D., Greenshields, K., Verschuuren, J. J., Jacobs, B. C., Rother, R. P., Plomp, J. J., and Willison, H. J. (2008) Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain 131, 1197–1208.

    Article  PubMed  Google Scholar 

  26. Fujii, S., and Hitomi, Y. (1981) New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim. Biophys. Acta 661, 342–345.

    CAS  PubMed  Google Scholar 

  27. Fujita, Y., Inoue, I., Inagi, R., Miyata, T., Shinzato, T., Sugiyama, S., Miyama, A., and Maeda, K. (1993) Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia. Nippon Jinzo Gakkai Shi 35, 393–397.

    CAS  PubMed  Google Scholar 

  28. Inagi, R., Miyata, T., Maeda, K., Sugiyama, S., Miyama, A., and Nakashima, I. (1991) FUT-175 as a potent inhibitor of C5/C3 convertase activity for production of C5a and C3a. Immunol. Lett. 27, 49–52.

    Article  CAS  PubMed  Google Scholar 

  29. Phongsisay, V., Susuki, K., Matsuno, K., Yamahashi, T., Okamoto, S., Funakoshi, K., Hirata, K., Shinoda, M., and Yuki, N. (2008) Complement inhibitor prevents disruption of sodium channel clusters in a rabbit model of Guillain-Barré syndrome. J. Neuroimmunol. 205, 101–104.

    Article  CAS  PubMed  Google Scholar 

  30. Gilbert, M., Brisson, J. R., Karwaski, M. F., Michniewicz, J., Cunningham, A. M., Wu, Y., Young, N. M., and Wakarchuk, W. W. (2000) Biosynthesis of ganglioside mimics in Campylobacter jejuni OH4384: identification of the glycosyltransferase genes, enzymatic synthesis of model compounds, and characterization of nanomole amounts by 600-MHz 1H and 13C NMR analysis. J. Biol. Chem. 275, 3896–3906.

    Article  CAS  PubMed  Google Scholar 

  31. van Belkum, A., van den Braak, N., Godschalk, P. C. R., Ang, W., Jacobs, B. C., Gilbert, M., Wakarchuk, W. W., Verbrugh, H., and Endtz, H. P. (2001) A Campylobacter jejuni gene associated with immune-mediated neuropathy. Nat. Med. 7, 752–753.

    Article  PubMed  Google Scholar 

  32. Nachamkin, I., Liu, J., Li, M., Ung, H., Moran, A. P., Prendergast, M. M., and Sheikh, K. (2002) Campylobacter jejuni from patients with Guillain-Barré syndrome preferentially expresses a GD1a-like epitope. Infect. Immun. 70, 5299–5303.

    Article  CAS  PubMed  Google Scholar 

  33. Parkhill, J., Wren, B. W., Mungall, K., Ketley, J. M., Churcher, C., Basham, D., Chillingworth, T., Davies, R. M., Feltwell, T., Holroyd, S., Jagels, K., Karlyshev, A. V., Moule, S., Pallen, M. J., Penn, C. W., Quail, M. A., Rajandream, M. A., Rutherford, K. M., van Vliet, A. H., Whitehead, S., and Barrell, B. G. (2000) The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403, 665–668.

    Article  CAS  PubMed  Google Scholar 

  34. Gilbert, M., Godschalk, P. C. R., Parker, C. T., Endtz, H. P., and Wakarchuk, W. W. (2005) Genetic bases for the variation in the lipooligosaccharide outer core of Campylobacter jejuni and possible association of glycosyltransferase genes with postinfectious neuropathies. In: Ketley J, Konkel M, editors. Campylobacter: Molecular and Cellular Biology. Norwich, UK: Horizon Scientific Press; pp. 219–248.

    Google Scholar 

  35. Parker, C. T., Horn, S. T., Gilbert, M., Miller, W. G., Woodward, D. L., and Mandrell, R. E. (2005) Comparison of Campylobacter jejuni lipooligosaccharide biosynthesis loci from a variety of sources. J. Clin. Microbiol. 43, 2771–2781.

    Article  CAS  PubMed  Google Scholar 

  36. Godschalk, P. C. R., Heikema, A. P., Gilbert, M., Komagamine, T., Ang, C. W., Glerum, J., Brochu, D., Li, J., Yuki, N., Jacobs, B. C., van Belkum, A., and Endtz, H. P. (2004) The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome. J. Clin. Invest. 114, 1659–1665.

    CAS  PubMed  Google Scholar 

  37. Chiba, A., Kusunoki, S., Obata, H., Machinami, R., and Kanazawa, I. (1993) Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies. Neurology 43, 1911–1917.

    CAS  PubMed  Google Scholar 

  38. Chiba, A., Kusunoki, S., Shimizu, T., and Kanazawa, I. (1992) Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann. Neurol. 31, 677–679.

    Article  CAS  PubMed  Google Scholar 

  39. Koga, M., Gilbert, M., Li, J., Koike, S., Takahashi, M., Furukawa, K., Hirata, K., and Yuki, N. (2005) Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry. Neurology 64, 1605–1611.

    Article  CAS  PubMed  Google Scholar 

  40. Kimoto, K., Koga, M., Odaka, M., Hirata, K., Takahashi, M., Li, J., Gilbert, M., and Yuki, N. (2006) Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies. Neurology 67, 1837–1843.

    Article  CAS  PubMed  Google Scholar 

  41. Nam Shin, J. E., Ackloo, S., Mainkar, A. S., Monteiro, M. A., Pang, H., Penner, J. L., and Aspinall, G. O. (1997) Lipo-oligosaccharides of Campylobacter jejuni serotype O:10: structures of core oligosaccharide regions from a bacterial isolate from a patient with the Miller-Fisher [sic] syndrome and from the serotype reference strain. Carbohydr. Res. 305, 223–232.

    Article  CAS  Google Scholar 

  42. Houliston, R. S., Koga, M., Li, J., Jarrell, H. C., Richards, J. C., Vitiazeva, V., Schweda, E. K., Yuki, N., and Gilbert, M. (2007) A Haemophilus influenzae strain associated with Fisher syndrome expresses a novel disialylated ganglioside mimic. Biochemistry 46, 8164–8171.

    Article  CAS  PubMed  Google Scholar 

  43. Koga, M., Takahashi, M., Masuda, M., Hirata, K., and Yuki, N. (2005) Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome. Neurology 65, 1376–1381.

    Article  CAS  PubMed  Google Scholar 

  44. Gilbert, M., Karwaski, M. F., Bernatchez, S., Young, N. M., Taboada, E., Michniewicz, J., Cunningham, A. M., and Wakarchuk, W. W. (2002) The genetic bases for the variation in the lipo-oligosaccharide of the mucosal pathogen, Campylobacter jejuni: biosynthesis of sialylated ganglioside mimics in the core oligosaccharide. J. Biol. Chem. 277, 327–337.

    Article  CAS  PubMed  Google Scholar 

  45. Yuki, N. (2007) Ganglioside mimicry and peripheral nerve disease. Muscle Nerve. 35, 691–711.

    Article  CAS  PubMed  Google Scholar 

  46. Gong, Y., Tagawa, Y., Lunn, M. P., Laroy, W., Heffer-Lauc, M., Li, C. Y., Griffin, J. W., Schnaar, R. L., and Sheikh, K. A. (2002) Localization of major gangliosides in the PNS: implications for immune neuropathies. Brain 125, 2491–2506.

    Article  CAS  PubMed  Google Scholar 

  47. Kusunoki, S., Chiba, A., and Kanazawa, I. (1999) Anti-GQ1b IgG antibody is associated with ataxia as well as ophthalmoplegia. Muscle Nerve. 22, 1071–1074.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The dedicated efforts of the scientific staff in my laboratory and our many external collaborators are greatly appreciated. I thank Dr. Keiichiro Susuki (Department of Neuroscience, Baylor College of Medicine) for his help with the figure preparations; and Drs. Bart C Jacobs (Departments of Neurology and Immunology, Erasmus MC), and Michel Gilbert (Institute for Biological Sciences, National Research Council Canada) for their critical reading and English editing of this review.

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  1. Departments of Neurology and Clinical Research, Niigata National Hospital, Niigata, Japan

    Nobuhiro Yuki

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  1. Inst. Biological Sciences, National Research Council Canada, Sussex Drive 100, Ottawa, K1A 0R6, Canada

    Jianjun Li

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Yuki, N. (2010). Human Gangliosides and Bacterial Lipo-oligosaccharides in the Development of Autoimmune Neuropathies. In: Li, J. (eds) Functional Glycomics. Methods in Molecular Biology, vol 600. Humana Press. https://doi.org/10.1007/978-1-60761-454-8_4

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  • DOI: https://doi.org/10.1007/978-1-60761-454-8_4

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