Skip to main content

Advertisement

SpringerLink
Log in

GQ1b-seronegative Fisher syndrome: clinical features and new serological markers

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

IgG anti-GQ1b antibodies are a powerful serological marker for the diagnosis of Fisher syndrome (FS), but little is known regarding serological markers in FS patients that do not have the autoantibodies. The authors analyzed IgG antibodies against gangliosides other than GQ1b, ganglioside complexes, and ganglioside-like lipo-oligosaccharide (LOS) of Campylobacter jejuni isolates from FS patients. We identified 24 (12%) patients with GQ1b-seronegative FS among 207 FS patients who had been referred to our laboratory for anti-ganglioside antibody testing. Patients with GQ1b-seronegative FS were male and had a history of antecedent gastrointestinal illness more frequently than FS patients with IgG anti-GQ1b antibodies. Other clinical features during the illness were not distinguishing for GQ1b-seronegative FS. Four (17%) of 24 patients with GQ1b-seronegative FS had IgG antibodies against single gangliosides such as GM1b, GD1a, or GT1a. Antibodies against GM1 and GT1a complex were detected in four GQ1b-seronegative FS patients, three of whom did not have antibodies against single gangliosides. Mass spectrometry analysis showed that C. jejuni isolates from FS patients had GD1c-, GalNAc-GM1b-, or GalNAc-GD1c-like LOS, and not GQ1b-like LOS, highlighting the utility of examining serum antibodies against these ganglioside mimics in GQ1b-seronegative FS patients. Seven (29%) had IgG antibodies against the LOS from C. jejuni strains expressing GD1c-, GalNAc-GM1b-, or GalNAc-GD1c-like LOS. These findings suggest that IgG antibodies against GM1b, GD1c, GalNAc-GM1b, and ganglioside complexes are serological markers for GQ1b-seronegative Fisher syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Chiba A, Kusunoki S, Obata H, Machinami R, 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

    Article  PubMed  CAS  Google Scholar 

  3. Willison HJ, Veitch J (1994) Immunoglobulin subclass distribution and binding characteristics of anti-GQ1b antibodies in Miller Fisher syndrome. J Neuroimmunol 50:159–165

    Article  PubMed  CAS  Google Scholar 

  4. Ito M, Kuwabara S, Odaka S, Misawa S, Koga M, Hirata K et al (2008) Bickerstaff’s brainstem encephalitis and Fisher syndrome form a continuous spectrum: clinical analysis of 581 cases. J Neurol 255:674–682

    Article  PubMed  CAS  Google Scholar 

  5. Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N (2000) Axonal Guillain-Barré syndrome: relation to ant-ganglioside antibodies and Campylobacter jejuni infection in Japan. Annu Neurol 48:624–631

    Article  CAS  Google Scholar 

  6. Ogawara K, Kuwabara S, Koga M, Mori M, Yuki N, Hattori T (2003) Anti-GM1b IgG antibody is associated with acute motor axonal neuropathy and Campylobacter jejuni infection. J Neurol Sci 210:41–45

    Article  PubMed  CAS  Google Scholar 

  7. Kaida K, Kanzaki M, Morita D, Kamakura K, Motoyoshi K, Hirakawa M et al (2006) Anti-ganglioside complex antibodies in Miller Fisher syndrome. J Neurol Neurosurg Psychiatry 77:1043–1046

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Nam Shin JE, Sckloo S, Mainkar AS, Monteiro MA, Pang H, Penner JL et al (1998) 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  Google Scholar 

  10. Kimoto K, Koga M, Odaka M, Hirata K, Takahashi M, Li J et al (2006) Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies. Neurology 67:1837–1843

    Article  PubMed  CAS  Google Scholar 

  11. Godschalk PCR, Kuijf ML, Li J, St Michael F, Ang CW, Jacobs BC et al (2007) Structural characterization of Campylobacter jejuni lipooligosaccharide outer cores associated with Guillain-Barré and Miller Fisher syndromes. Infect Immun 75:1245–1254

    Article  PubMed  CAS  Google Scholar 

  12. Yuki N, Tagawa Y, Irie F, Hirabayashi Y, Handa S (1997) Close association of Guillain-Barré syndrome with antibodies to minor monosialogangliosides GM1b and GM1α. J Neuroimmunol 74:30–34

    Article  PubMed  CAS  Google Scholar 

  13. Koga M, Gilbert M, Takahashi M, Li J, Koike S, Hirata K et al (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  PubMed  CAS  Google Scholar 

  14. Li J, Koga M, Brochu D, Yuki N, Chan K, Gilbert M (2005) Electrophoresis-assisted open-tubular liquid chromatography/mass spectrometry for the analysis of lipooligosaccharide expressed by Campylobacter jejuni. Electrophoresis 26:3360–3368

    Article  PubMed  CAS  Google Scholar 

  15. Parker CT, Gilbert M, Yuki N, Endtz HP, Mandrell RE (2008) Characterization of lipo-oligosaccharide-biosynthetic loci of Campylobacter jejuni reveals new lipooligosaccharide classes: evidence of mosaic organizations. J Bacteriol 190:5681–5689

    Article  PubMed  CAS  Google Scholar 

  16. Houliston RS, Vinogradov E, Dzieciatkowska M, Li J, St Michael F, Karwaski MF et al (2011) The lipooligosaccharide of Campylobacter jejuni: similarity with multiple types of mammalian glycans beyond gangliosides. J Biol Chem 286:12361–12370

    Article  PubMed  CAS  Google Scholar 

  17. Houliston RS, Endtz HP, Yuki N, Li J, Jarrell HC, Koga M et al (2006) Identification of a sialate O-acetyltransferase from Campylobacter jejuni: demonstration of direct transfer to the C-9 position of terminal α-2, 8-linked sialic acid. J Biol Chem 281:11480–11486

    Article  PubMed  CAS  Google Scholar 

  18. Dzieciatkowska M, Brochu D, van Belkum A, Heikema AP, Yuki N, Houliston RS et al (2007) Mass spectrometric analysis of intact lipooligosaccharide: direct evidence for O-acetylated sialic acids and discovery of O-linked glycine expressed by Campylobacter jejuni. Biochemistry 46:14704–14714

    Article  PubMed  CAS  Google Scholar 

  19. Szymanski CM, St Michael F, Jarrell HC, Li J, Gilbert M, Larocque S et al (2003) Detection of conserved N-linked glycans and phase-variable lipooligosaccharides and capsules for Campylobacter cells by mass spectrometry and high resolution magic angle spinning NMR spectroscopy. J Biol Chem 278:24509–24520

    Article  PubMed  CAS  Google Scholar 

  20. St Michael F, Szymanski CM, Li J, Chan KH, Khieu NH, Larocque S et al (2002) The structures of the lipooligosaccharide and capsule polysaccharide of Campylobacter jejuni genome sequenced strain NCTC 11168. Eur J Biochem 269:5119–5136

    Article  PubMed  CAS  Google Scholar 

  21. Hitchcock PJ, Brown TM (1983) Morphological heterogeneity among Salmonella lopopolysaccharide chemotypes in silver-stained polyacrylamide gels. J Bacteriol 154:269–277

    PubMed  CAS  Google Scholar 

  22. Odaka M, Yuki N, Hirata K (2001) Anti-GQ1b IgG antibody syndrome: clinical and immunological range. J Neurol Neurosurg Psychiatry 70:50–55

    Article  PubMed  CAS  Google Scholar 

  23. Vincent A, Leite MI (2005) Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18:519–525

    Article  PubMed  CAS  Google Scholar 

  24. Hayashi Y, Koga M, Takahashi M, Uchida A, Yuki N (2001) Anti-GQ1b-negative case of overlapping Fisher’s and Guillain-Barré syndromes after Campylobacter jejuni (PEN 19) enteritis. Rinsho Shinkeigaku 41:801–804 (in Japanese)

    PubMed  CAS  Google Scholar 

  25. Tan H, Caner İ, Deniz O, Büyükavcı M (2003) Miller Fisher syndrome with negative anti-GQ1b immunoglobulin G antibodies. Pediatr Neurol 29:349–350

    Article  PubMed  Google Scholar 

  26. Gentilea S, Messinab M, Raineroa I, Lo Giudicea R, De Martinoa P, Pinessia L (2006) Miller Fisher syndrome associated with Burkitt’s lymphoma. Eur J Neurol 13:423

    Article  Google Scholar 

  27. Akinci G, Oztura I, Hiz-Kurul S (2010) Anti-GQ1b-negative Miller Fisher syndrome presented with one-sided horizontal gaze palsy. Turk J Pediart 52:317–320

    Google Scholar 

  28. Tatsumoto M, Koga M, Gilbert M, Odaka M, Hirata K, Kuwabara S et al (2006) Spectrum of neurological diseases associated with antibodies to minor gangliosides GM1b and GalNAc-GD1a. J Neuroimmunol 177:201–208

    Article  PubMed  CAS  Google Scholar 

  29. Koga M, Yoshino H, Morimatsu M, Yuki N (2003) Anti-GT1a IgG in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 72:767–771

    Article  Google Scholar 

  30. Halstead SK, Zitman FM, Humphreys PD, Greenshields K, Verschuuren JJ, Jacobs BC et al (2008) Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain 131:1197–1208

    Article  PubMed  Google Scholar 

  31. Kanzaki M, Kaida K, Ueda M, Morita D, Hirakawa M, Motoyoshi K et al (2008) Ganglioside complexes containing GQ1b as targets in Miller Fisher and Guillain-Barré syndromes. J Neurol Neurosurg Psychiatry 79:1148–1152

    Article  PubMed  CAS  Google Scholar 

  32. Ilyas AA, Li SC, Chou DKH, Li YT, Jungalwala FB, Dalakas MC et al (1988) Gangliosides GM2, IV4GalNAcGM1b, and IV4GalNAcGD1a as antigens for monoclonal immunoglobulin M in neuropathy associated with gammopathy. J Biol Chem 263:4369–4373

    PubMed  CAS  Google Scholar 

  33. Yuki N, Taki T, Handa S (1996) Antibody to GalNAc-GD1a and GalNAc-GM1b in Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis. J Neuroimmunol 71:155–161

    Article  PubMed  CAS  Google Scholar 

  34. Ortiz N, Rosa R, Gallardo E, Illa I, Tomas J, Aubry J et al (2001) IgM monoclonal antibody against terminal moiety of GM2, GalNAc-GD1a and GalNAc-GM1b from a pure motor chronic demyelinating polyneuropathy patient: effects on neurotransmitter release. J Neuroimmunol 119:114–123

    Article  PubMed  CAS  Google Scholar 

  35. Chikakiyo H, Kunishige M, Yoshino H, Asano A, Sumitomo Y, Endo I et al (2005) Delayed motor and sensory neuropathy in a patient with brainstem encephalitis. J Neurol Sci 234:105–108

    Article  PubMed  Google Scholar 

  36. Odaka M, Yuki N, Tatsumoto M, Tateno M, Hirata K (2004) Ataxic Guillain-Barré syndrome associated with anti-GM1b and anti-GalNAc-GD1a antibodies. J Neurol 251:24–29

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr Masaaki Odaka (Dokkyo Medical University) for proving detailed data from a previous study. We thank Denis Brochu (National Research Council Canada, Institute for Biological Sciences) for help with the analysis of the LOS outer core structures and Marie-France Karwaski (National Research Council Canada, Institute for Biological Sciences) for DNA sequencing of LOS biosynthesis genes.

Dr Koga received a grant from the Kimi Imai Memorial Foundation for Neuromuscular Diseases and a Grant-in-Aid for Scientific Research (C) (KAKENHI 20590446) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Drs Gilbert, Li, Takahashi, and Hirata report no disclosures. Dr Kanda received a Research Grant for Neuroimmunological Diseases from the Ministry of Health, Labour and Welfare of Japan. Dr Yuki received a grant from National Medical Research Council (IRG 10 Nov 086), Ministry of Health and Yong Loo School of Medicine start-up grant (Nobuhiro Yuki) in Singapore.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Minami-kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan

    Michiaki Koga & Takashi Kanda

  2. Department of Neurology, Dokkyo Medical University, Tochigi, Japan

    Michiaki Koga, Koichi Hirata & Nobuhiro Yuki

  3. Institute for Biological Sciences, National Research Council Canada, Ottawa, ON, Canada

    Michel Gilbert & Jianjun Li

  4. Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan

    Masaki Takahashi

  5. Departments of Microbiology and Medicine, National University of Singapore, Science Drive 2, Block MD4A, Level 5, Singapore, 17597, Singapore

    Nobuhiro Yuki

Authors
  1. Michiaki Koga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michel Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koichi Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nobuhiro Yuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michiaki Koga or Nobuhiro Yuki.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koga, M., Gilbert, M., Takahashi, M. et al. GQ1b-seronegative Fisher syndrome: clinical features and new serological markers. J Neurol 259, 1366–1374 (2012). https://doi.org/10.1007/s00415-011-6360-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6360-y

Keywords

Search

Navigation