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PMID: 15578098 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome.

The Journal of clinical investigation ·Vol. 114 ·No. 11 ·2004-12-00 ·Pages 1659-65

Godschalk PC, Heikema AP, Gilbert M, Komagamine T, Ang CW, Glerum J, Brochu D, Li J, Yuki N, Jacobs BC, van Belkum A, Endtz HP

Abstract

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

MeSH Terms
Animals Autoantibodies/biosynthesis Biomarkers Campylobacter jejuni/chemistry,genetics Carbohydrate Conformation Cross Reactions Gangliosides/chemistry,immunology Genes, Bacterial Guillain-Barre Syndrome/immunology Humans Lipopolysaccharides/biosynthesis,chemistry Mice Molecular Mimicry Molecular Sequence Data Mutation N-Acetylneuraminic Acid/chemistry,immunology
Chemicals
Autoantibodies Biomarkers Gangliosides Lipopolysaccharides lipid-linked oligosaccharides N-Acetylneuraminic Acid
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Godschalk Peggy C R
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [email protected]
Heikema Astrid P
Gilbert Michel
Komagamine Tomoko
Ang C Wim
Glerum Jobine
Brochu Denis
Li Jianjun
Yuki Nobuhiro
Jacobs Bart C
van Belkum Alex
Endtz Hubert P
References (37)
37 references, click to expand
  1. Structure and conserved characteristics of Campylobacter jejuni lipopolysaccharides.
    J Infect Dis. 1997 Dec;176 Suppl 2:S115-21 PMID: 9396693
  2. Evidence for acquisition of the lipooligosaccharide biosynthesis locus in Campylobacter jejuni GB11, a strain isolated from a patient with Guillain-Barré syndrome, by horizontal exchange.
    Infect Immun. 2004 Feb;72(2):1162-5 PMID: 14742567
  3. 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 (1)h and (13)c NMR analysis.
    J Biol Chem. 2000 Feb 11;275(6):3896-906 PMID: 10660542
  4. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies.
    Neurology. 1993 Oct;43(10):1911-7 PMID: 8413947
  5. In vivo phase variation and serologic response to lipooligosaccharide of Campylobacter jejuni in experimental human infection.
    Infect Immun. 2004 Feb;72(2):916-22 PMID: 14742536
  6. Multiple N-acetyl neuraminic acid synthetase (neuB) genes in Campylobacter jejuni: identification and characterization of the gene involved in sialylation of lipo-oligosaccharide.
    Mol Microbiol. 2000 Mar;35(5):1120-34 PMID: 10712693
  7. The structures of the lipooligosaccharide and capsule polysaccharide of Campylobacter jejuni genome sequenced strain NCTC 11168.
    Eur J Biochem. 2002 Nov;269(21):5119-36 PMID: 12392544
  8. Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
    Nat Struct Mol Biol. 2004 Feb;11(2):163-70 PMID: 14730352
  9. Molecular characterization of Campylobacter jejuni from patients with Guillain-Barré and Miller Fisher syndromes.
    J Clin Microbiol. 2000 Jun;38(6):2297-301 PMID: 10834992
  10. Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganglioside.
    Ann Neurol. 2001 Jun;49(6):712-20 PMID: 11409422
  11. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.
    Nature. 2000 Feb 10;403(6770):665-8 PMID: 10688204
  12. Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10662-7 PMID: 8855236
  13. Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes.
    Lancet Infect Dis. 2001 Aug;1(1):29-37 PMID: 11871407
  14. Molecular mimicry and autoimmunity.
    N Engl J Med. 1999 Dec 30;341(27):2068-74 PMID: 10615080
  15. Deciphering Campylobacter jejuni cell surface interactions from the genome sequence.
    Curr Opin Microbiol. 2001 Feb;4(1):35-40 PMID: 11173031
  16. Comparison of Campylobacter jejuni isolates implicated in Guillain-Barré syndrome and strains that cause enteritis by a DNA microarray.
    Infect Immun. 2004 Feb;72(2):1199-203 PMID: 14742576
  17. Chemical characterization of Campylobacter jejuni lipopolysaccharides containing N-acetylneuraminic acid and 2,3-diamino-2,3-dideoxy-D-glucose.
    J Bacteriol. 1991 Jan;173(2):618-26 PMID: 1987154
  18. Sequence typing confirms that Campylobacter jejuni strains associated with Guillain-Barré and Miller-Fisher syndromes are of diverse genetic lineage, serotype, and flagella type.
    J Clin Microbiol. 2001 Sep;39(9):3346-9 PMID: 11526174
  19. Close association of Guillain-Barré syndrome with antibodies to minor monosialogangliosides GM1b and GM1 alpha.
    J Neuroimmunol. 1997 Apr;74(1-2):30-4 PMID: 9119976
  20. Structure of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity and clinical features of Guillain-Barré and Miller Fisher patients.
    Infect Immun. 2002 Mar;70(3):1202-8 PMID: 11854201
  21. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia).
    N Engl J Med. 1956 Jul 12;255(2):57-65 PMID: 13334797
  22. High-affinity anti-ganglioside IgG antibodies raised in complex ganglioside knockout mice: reexamination of GD1a immunolocalization.
    J Neurochem. 2000 Jul;75(1):404-12 PMID: 10854286
  23. The Guillain-Barré syndrome: a true case of molecular mimicry.
    Trends Immunol. 2004 Feb;25(2):61-6 PMID: 15102364
  24. Synthetic disialylgalactose immunoadsorbents deplete anti-GQ1b antibodies from autoimmune neuropathy sera.
    Brain. 2004 Mar;127(Pt 3):680-91 PMID: 14960498
  25. A Campylobacter jejuni gene associated with immune-mediated neuropathy.
    Nat Med. 2001 Jul;7(7):752-3 PMID: 11433317
  26. Immunoproliferative small intestinal disease associated with Campylobacter jejuni.
    N Engl J Med. 2004 Jan 15;350(3):239-48 PMID: 14724303
  27. Sialylation of lipooligosaccharide cores affects immunogenicity and serum resistance of Campylobacter jejuni.
    Infect Immun. 2000 Dec;68(12):6656-62 PMID: 11083778
  28. The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.
    Neurology. 1998 Oct;51(4):1110-5 PMID: 9781538
  29. Tolerance to self gangliosides is the major factor restricting the antibody response to lipopolysaccharide core oligosaccharides in Campylobacter jejuni strains associated with Guillain-Barré syndrome.
    Infect Immun. 2002 Sep;70(9):5008-18 PMID: 12183547
  30. Detection of conserved N-linked glycans and phase-variable lipooligosaccharides and capsules from campylobacter cells by mass spectrometry and high resolution magic angle spinning NMR spectroscopy.
    J Biol Chem. 2003 Jul 4;278(27):24509-20 PMID: 12716884
  31. Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome.
    Ann Neurol. 1996 Aug;40(2):181-7 PMID: 8773599
  32. Phase variation of Campylobacter jejuni 81-176 lipooligosaccharide affects ganglioside mimicry and invasiveness in vitro.
    Infect Immun. 2002 Feb;70(2):787-93 PMID: 11796612
  33. A case of Guillain-Barré syndrome following a family outbreak of Campylobacter jejuni enteritis.
    J Neuroimmunol. 2000 Nov 1;111(1-2):229-33 PMID: 11063843
  34. A PCR-based strategy for the rapid construction of defined bacterial deletion mutants.
    Biotechniques. 1994 Jun;16(6):994-6 PMID: 8074885
  35. Iron-responsive gene regulation in a campylobacter jejuni fur mutant.
    J Bacteriol. 1998 Oct;180(20):5291-8 PMID: 9765558
  36. 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. 2002 Jan 4;277(1):327-37 PMID: 11689567
  37. Peripheral neuropathies and anti-glycolipid antibodies.
    Brain. 2002 Dec;125(Pt 12):2591-625 PMID: 12429589
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI15707
Email
[email protected]
Published
2004-12-00
Pages
1659-65
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC529276
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI15707 PMC Full Text View journal details
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