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

被引:175
作者
Godschalk, PCR
Heikema, AP
Gilbert, M
Komagamine, T
Ang, CW
Glerum, J
Brochu, D
Li, JJ
Yuki, N
Jacobs, BC
van Belkum, A
Endtz, HP
机构
[1] Univ Med Ctr, Dept Med Microbiol & Infect Dis, Erasmus MC, NL-3015 GD Rotterdam, Netherlands
[2] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada
[3] Dokkyo Univ, Sch Med, Dept Neurol, Shimotsuga, Tochigi, Japan
[4] Univ Med Ctr, Dept Neurol, Erasmus MC, NL-3015 GD Rotterdam, Netherlands
[5] Univ Med Ctr, Dept Immunol, Erasmus MC, NL-3015 GD Rotterdam, Netherlands
关键词
D O I
10.1172/JCI200415707
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 ganghoside-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.
引用
收藏
页码:1659 / 1665
页数:7
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