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The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome
Peggy C.R. Godschalk, … , Alex van Belkum, Hubert P. Endtz
Peggy C.R. Godschalk, … , Alex van Belkum, Hubert P. Endtz
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1659-1665. https://doi.org/10.1172/JCI15707.
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Article Microbiology

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

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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-Barré 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.

Authors

Peggy C.R. Godschalk, Astrid P. Heikema, Michel Gilbert, Tomoko Komagamine, C. Wim Ang, Jobine Glerum, Denis Brochu, Jianjun Li, Nobuhiro Yuki, Bart C. Jacobs, Alex van Belkum, Hubert P. Endtz

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Figure 1

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Genetic organization of the 5 different classes of the C. jejuni LOS bio...
Genetic organization of the 5 different classes of the C. jejuni LOS biosynthesis locus. The distance between the scale marks is 1 kb. The direction of the arrows indicates the direction of transcription. Corresponding homologous genes have the same number with a letter for the LOS locus class added. For orf1c and orf13c the corresponding Cj gene numbers of the “genome” strain NCTC 11168 are given. The 5 LOS classes are based on DNA sequences of the following strains (GenBank accession number): class A: OH4384 (AF130984), OH4382 (AF167345), HS:4 (AF215659), HS:10 (AF400048), HS:19 (AF167344), HS:41 (AY044868); class B: HS:23 (AF401529), HS:36 (AF401528); class C: NCTC 11168 (AL139077), HS:1 (AY044156), HS:2 (AF400047); class D: LIO87 (AF400669); class E: 81116 (AF343914 and AJ131360). The proposed functions for the orfs are described in Supplemental Table 1.

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