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Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants

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Abstract

Anti-ganglioside autoantibodies of the IgG type are detected in a half of patients with Guillain-Barré syndrome (GBS), and their detection strongly supports the diagnosis of GBS. In contrast, anti-ganglioside IgM antibodies are also often detected in GBS patients, but it remains unclear whether IgM antibodies indicate a diagnosis of GBS. We identified four GBS patients (3.3 %) who tested positive for IgM antibodies but negative for IgG antibodies among 122 patients with GBS and its variants. These four patients were all adolescents or young adults (age 13–22 years), experienced preceding gastrointestinal symptoms, and had serological and/or bacterial evidence of recent Campylobacter jejuni enteritis. Serum IgG reacted strongly with the lipo-oligosaccharide (LOS) of the C. jejuni isolates from these patients’ stool specimens. Thin-layer chromatography with immunostaining showed that their serum IgG reacted with resorcinol-positive portion of LOS, suggesting that these patients had IgG autoantibodies against sialic acid-containing epitopes, probably unrecognized ganglioside-like structures on the bacterial LOS. We also examined anti-ganglioside autoantibodies in 22 patients with C. jejuni enteritis without subsequent neurological disorders and detected IgM antibodies in seven (32 %) patients. Our data indicate that anti-ganglioside IgM antibodies can be detected in C. jejuni enteritis without complication of GBS, and that the detection of anti-ganglioside IgM antibodies does not always support a diagnosis of GBS. IgG autoantibodies against unrecognized gangliosides might play a role in the development of disease in patients with GBS in whom only anti-ganglioside IgM antibodies are detected by routine clinical testing.

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References

  1. Uncini A, Kuwabara S (2012) Electrodiagnostic criteria for Guillain-Barrè syndrome: a critical revision and the need for an update. Clin Neurophysiol 123:1487–1495

    Article  PubMed  Google Scholar 

  2. Yuki N, Hartung HP (2012) Guillain-Barré syndrome. N Engl J Med 366:2294–2304

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. 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  CAS  PubMed  Google Scholar 

  5. Jacobs BC, Rothbarth PH, van der Meché FG, Herbrink P, Schmitz PI, de Klerk MA et al (1998) The spectrum of antecedent infections in Guillain-Barré syndrome: a case–control study. Neurology 51:1110–1115

    Article  CAS  PubMed  Google Scholar 

  6. Kaida K (2013) Pathogenic roles of antiganglioside antibodies in immune-mediated neuropathies. Clin Exp Neuroimmunol 4:60–69

    Article  CAS  Google Scholar 

  7. Nobile-Orazio E, Gallia F, Terenghi F, Allaria S, Giannotta C, Carpo M (2008) How useful are anti-neural IgM antibodies in the diagnosis of chronic immune-mediated neuropathies? J Neurol Sci 266:156–163

    Article  CAS  PubMed  Google Scholar 

  8. Irie S, Saito T, Nakamura K, Kanazawa N, Ogino M, Nukazawa T et al (1996) Association of anti-GM2 antibodies in Guillain-Barré syndrome with acute cytomegalovirus infection. J Neuroimmunol 68:19–26

    Article  CAS  PubMed  Google Scholar 

  9. Jacobs BC, van Doorn PA, Groeneveld JH, Tio-Gillen AP, van der Meché FG (1997) Cytomegalovirus infections and anti-GM2 antibodies in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 62:641–643

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Yuki N, Tagawa Y (1998) Acute cytomegalovirus infection and IgM anti-GM2 antibody. J Neurol Sci 154:14–17

    Article  CAS  PubMed  Google Scholar 

  11. Kusunoki S, Chiba A, Hitoshi S, Takizawa H, Kanazawa I (1995) Anti-Gal-C antibody in autoimmune neuropathies subsequent to mycoplasma infection. Muscle Nerve 18:409–413

    Article  CAS  PubMed  Google Scholar 

  12. Ang CW, Tio-Gillen AP, Groen J, Herbrink P, Jacobs BC, Van Koningsveld R (2002) Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae infections in Guillain-Barré syndrome. J Neuroimmunol 130:179–183

    Article  CAS  PubMed  Google Scholar 

  13. Ang CW, Jacobs BC, Brandenburg AH, Laman JD, van der Meché FG (2000) Cross-reactive antibodies against GM2 and CMV-infected fibroblasts in Guillain-Barré syndrome. Neurology 54:1453–1458

    Article  CAS  PubMed  Google Scholar 

  14. Kusunoki S, Shiina M, Kanazawa I (2001) Anti-Gal-C antibodies in GBS subsequent to mycoplasma infection: evidence of molecular mimicry. Neurology 57:736–738

    Article  CAS  PubMed  Google Scholar 

  15. Asbury AK, Cornblath DR (1990) Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol 27 (suppl):S21–S24

    Article  Google Scholar 

  16. Koga M, Gilbert M, Takahashi M, Li J, Hirata K, Kanda T et al (2012) GQ1b-seronegative Fisher syndrome: clinical features and new serological markers. J Neurol 259:1366–1374

    Article  CAS  PubMed  Google Scholar 

  17. Koga M, Kusunoki S, Kaida K, Uehara R, Nakamura Y, Kohriyama T et al (2012) Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis: epidemiological and clinical characteristics. J Neurol Neurosurg Psychiatry 83:1210–1215

    Article  PubMed  Google Scholar 

  18. 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  CAS  PubMed  Google Scholar 

  19. Takahashi M, Koga M, Yokoyama K, Yuki N (2005) Epidemiology of Campylobacter jejuni-isolated Guillain-Barré and Fisher syndromes in Japan. J Clin Microbiol 43:335–339

    Article  PubMed Central  PubMed  Google Scholar 

  20. 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-Barre syndrome after Campylobacter jejuni enteritis. J Infect Dis 193:547–555

    Article  CAS  PubMed  Google Scholar 

  21. Visser LH, van der Meché FG, Meulstee J, Rothbarth PP, Jacobs BC, Schmitz PI et al (1996) Cytomegalovirus infection and Guillain-Barré syndrome: the clinical, electrophysiologic, and prognostic features. Neurology 47:668–673

    Article  CAS  PubMed  Google Scholar 

  22. Jacobs BC, van Doorn PA, Schmitz PI, Tio-Gillen AP, Herbrink P, Visser LH et al (1996) Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome. Ann Neurol 40:181–187

    Article  CAS  PubMed  Google Scholar 

  23. Kuwabara S, Nakata M, Sung JY, Mori M, Kato N, Hattori T et al (2002) Hyperreflexia in axonal Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis. J Neurol Sci 25:297–299

    Google Scholar 

  24. 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  CAS  PubMed  Google Scholar 

  25. Svennerholm L (1957) Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method. Biochim Biophys Acta 24:604–611

    Article  CAS  PubMed  Google Scholar 

  26. Sawai S, Satoh M, Mori M, Misawa S, Sogawa K, Kazami T et al (2014) Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome. Neurology 83:113–117

    Article  CAS  PubMed  Google Scholar 

  27. Miyaji K, Devaux J, Yuki N (2014) Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome. Neurology 83:2314

    Article  PubMed  Google Scholar 

  28. Ilyas AA, Li SC, Chou DK, Li YT, Jungalwala FB, Dalakas MC, Quarles RH (1988) Gangliosides GM2, IV4GalNAcGM1b, and IV4GalNAcGC1a as antigens for monoclonal immunoglobulin M in neuropathy associated with gammopathy. J Biol Chem 263:4369–4373

    CAS  PubMed  Google Scholar 

  29. Kaida K, Kusunoki S, Kamakura K, Motoyoshi K, Kanazawa I (2003) GalNAc-GD1a in human peripheral nerve: target sites of anti-ganglioside antibody. Neurology 61:465–470

    Article  CAS  PubMed  Google Scholar 

  30. Yoshino H, Utsunomiya I, Taguchi K, Ariga T, Nagaoka T, Aoyagi H (2005) GalNAc-GD1a is localized specifically in ventral spinal roots, but not in dorsal spinal roots. Brain Res 1057:177–180

    Article  CAS  PubMed  Google Scholar 

  31. Kaida K, Kusunoki S, Kamakura K, Motoyoshi K, Kanazawa I (2001) Guillain-Barré syndrome with IgM antibody to the ganglioside GalNAc-GD1a. J Neuroimmunol 113:260–267

    Article  CAS  PubMed  Google Scholar 

  32. Kusunoki S, Chiba A, Kon K, Ando S, Arisawa K, Tate A (1994) N-acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain-Barré syndrome. Ann Neurol 35:570–576

    Article  CAS  PubMed  Google Scholar 

  33. Kaida K, Kusunoki S, Kamakura K, Motoyoshi K, Kanazawa I (2000) Guillain-Barré syndrome with antibody to a ganglioside, N-acetylgalactosaminyl GD1a. Brain 123:116–124

    Article  PubMed  Google Scholar 

  34. Kaji R, Kusunoki S, Mizutani K, Oka N, Kojima Y, Kohara N et al (2000) Chronic motor axonal neuropathy associated with antibodies monospecific for N-acetylgalactosaminyl GD1a. Muscle Nerve 23:702–706

    Article  CAS  PubMed  Google Scholar 

  35. Taguchi K, Ren J, Utsunomiya I, Aoyagi H, Fujita N, Ariga T (2004) Neurophysiological and immunohistochemical studies on Guillain-Barré syndrome with IgG anti-GalNAc-GD1a antibodies-effects on neuromuscular transmission. J Neurol Sci 225:91–98

    Article  CAS  PubMed  Google Scholar 

  36. Kamakura K, Kaida K, Kusunoki S, Miyamoto N, Masaki T, Nakamura R (2005) Harmful effects of anti-GalNAc-GD1a antibodies and TNF-alpha on rat dorsal root ganglia. J Peripher Nerv Syst 10:190–201

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Dr Koga received a Grant-in-Aid for Scientific Research (C) (KAKENHI 15K08464) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Prof Kanda received a Research Grant for Neuroimmunological Diseases from the Ministry of Health, Labour and Welfare of Japan.

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The study protocol was approved by the Institutional Ethics Committee at Yamaguchi University Hospital.

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Correspondence to Michiaki Koga.

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Koga, M., Takahashi, M., Yokoyama, K. et al. Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants. J Neurol 262, 1954–1960 (2015). https://doi.org/10.1007/s00415-015-7806-4

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  • DOI: https://doi.org/10.1007/s00415-015-7806-4

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