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Immunoglobulin KM allotypes are associated with the prevalence of autoantibodies to GD1a ganglioside, but not with susceptibility to the disease, in Japanese patients with Guillain–Barré syndrome

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Abstract

Guillain–Barré syndrome (GBS), an autoimmune disease of the peripheral nervous system, is associated with antecedent Campylobacter jejuni infection. GM and KM allotypes—genetic markers of immunoglobulin γ and κ chains, respectively—are implicated in the etiopathogenesis of several autoimmune diseases. To determine if GM/KM phenotypes are associated with GBS and influence antibody responses to C. jejuni and to GM1 and GD1a gangliosides, 72 Japanese GBS patients and 73 controls were allotyped for several GM and KM markers. Sera from patients were characterized for antibodies to C. jejuni, GM1, and GD1a. The distribution of KM phenotypes was significantly different in patients with anti-GD1a ganglioside antibodies from those who lacked these antibodies (P=0.029). No other significant associations were found. These results suggest that KM allotypes are not risk factors for developing GBS, but contribute significantly to the generation of autoimmune responses to GD1a ganglioside in patients with this disease.

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References

  1. Yuki N (2001) Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes. Lancet Infect Dis 1:29–37

    Article  PubMed  CAS  Google Scholar 

  2. McCarthy N, Giesecke J (2001) Incidence of Guillain–Barré syndrome following infection with Campylobacter jejuni. Am J Epidemiol 153:610–614

    Article  PubMed  CAS  Google Scholar 

  3. Pandey JP, Vedeler CA (2003) Immunoglobulin KM genes in Guillain–Barré syndrome. Neurogenetics 4:147–149

    PubMed  Google Scholar 

  4. Yuki N, Taki T, Takahashi M, Saito K, Tai T, Miyatake T, Handa S (1994) Penner's serotype 4 of Campylobacter jejuni has a lipopolysaccharide that bears a GM1 ganglioside epitope as well as one that bears a GD1a epitope. Infect Immun 62:2101–2103

    PubMed  CAS  Google Scholar 

  5. Yuki N, Susuki K, Koga M, Nishimoto Y, Odaka M, Hirata K, Taguchi K, Miyatake T, Furukawa K, Kobata T, 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  PubMed  CAS  Google Scholar 

  6. Steinberg AG, Cook CE (1981) The distribution of human immunoglobulin allotypes. Oxford University Press, New York

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Vyas GN, Fudenberg HH, Pretty HM, Gold ER (1968) A new rapid method for genetic typing of human immunoglobulins. J Immunol 100:274–279

    PubMed  CAS  Google Scholar 

  9. Schanfield MS, van Loghem E (1986) Human immunoglobulin allotypes. In: Weir DM (ed) Handbook of experimental immunology, 4th edn, vol 3, Genetics and molecular immunology. Blackwell, Boston, pp 94.1–94.18

    Google Scholar 

  10. Shows TB, McAlpine PJ, Boucheix C, Collins FS, Conneally PM, Frezal J, Gershowitz H, Goodfellow PN, Hall JG et al (1987) Guidelines for human gene nomenclature. An international system for human gene nomenclature (ISGN). Cytogenet Cell Genet 46:11–28

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Pandey JP, Blaser MJ (1986) Heterozygosity at the Km locus associated with humoral immunity to Campylobacter jejuni. Exp Clin Immunogenet 3:49–53

    PubMed  CAS  Google Scholar 

  13. Pandey JP (2001) Immunoglobulin GM and KM allotypes and vaccine immunity. Vaccine 19:613–617

    Article  Google Scholar 

  14. Whittingham S, Propert DN, Mackay IR (1984) A strong association between the nuclear antibody anti-La (SS-B) and the kappa chain allotype Km(1). Immunogenetics 19:295–299

    Article  PubMed  CAS  Google Scholar 

  15. Hoffman RW, Sharp GC, Irvin WS, Anderson SK, Hewett JE, Pandey JP (1991) Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. Arthritis Rheum 34:453–458

    Article  PubMed  CAS  Google Scholar 

  16. Kameda H, Pandey JP, Kaburaki J, Inoko H, Kuwana M (1998) Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and KM genes on anticentromere antibody production. Ann Rheum Dis 57:366–370

    PubMed  CAS  Google Scholar 

  17. Pandey JP, Page GP, Silver RM, LeRoy EC, Bona CA (2001) Anti-fibrillin-1 autoantibodies in systemic sclerosis are GM and KM allotype restricted. Exp Clin Immunogenet 18:123–129

    Article  PubMed  CAS  Google Scholar 

  18. Morahan G, Berek C, Miller JFAP (1983) An idiotypic determinant formed by both immunoglobulin constant and variable regions. Nature 301:720–722

    Article  PubMed  CAS  Google Scholar 

  19. Moxley G, Gibbs RS (1992) Polymerase chain reaction-based genotyping for allotypic markers of immunoglobulin kappa shows allelic association of Km with kappa variable segment. Genomics 13:104–108

    Article  PubMed  CAS  Google Scholar 

  20. Pritsch O, Hudry-Clergeon G, Buckle M, Petillot Y, Bouvet JP, Gagnon J, Dighiero G (1996) Can immunoglobulin CH1 constant region domain modulate antigen binding affinity of antibodies? J Clin Invest 98:2235–2243

    Article  PubMed  CAS  Google Scholar 

  21. Torres M, May R, Scharff MD, Casadevall A (2005) Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype. J Immunol 174:2132–2142

    PubMed  CAS  Google Scholar 

  22. Wandstrat A, Wakeland E (2001) The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nat Immunol 2:802–809

    Article  PubMed  CAS  Google Scholar 

  23. Magira EE, Papaioakim M, Nachamkin I, Asbury AK, Li CY, Ho TW, Griffin JW, McKhann GM, Monos DS (2003) Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain–Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP. J Immunol 170:3074–3080

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the US Department of Energy cooperative agreement DE-FC09-02CH11109 and by a grant-in-aid for Scientific Research (B) (KAKENHI 14370210 to N.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Keith Rocca and Brenda Steadham for excellent technical assistance.

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  1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425-2230, USA

    Janardan P. Pandey

  2. Department of Neurology, Dokkyo University School of Medicine, Tochigi, Japan

    Michiaki Koga & Nobuhiro Yuki

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  1. Janardan P. Pandey
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  2. Michiaki Koga
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  3. Nobuhiro Yuki
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Correspondence to Janardan P. Pandey.

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Pandey, J.P., Koga, M. & Yuki, N. Immunoglobulin KM allotypes are associated with the prevalence of autoantibodies to GD1a ganglioside, but not with susceptibility to the disease, in Japanese patients with Guillain–Barré syndrome. Neurogenetics 6, 225–228 (2005). https://doi.org/10.1007/s10048-005-0022-0

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  • DOI: https://doi.org/10.1007/s10048-005-0022-0

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