The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome
The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome
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DOI：
10.1172/jci200415707
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发表时间：
2004-12-01
影响因子：
15.9
通讯作者：
Endtz, HP
中科院分区：
文献类型：
--
作者：
Godschalk, PCR;Heikema, AP;Endtz, HP
空肠弯曲杆菌脂寡糖（LOS）与神经组织中的神经节苷脂的分子模拟被认为可诱导交叉反应抗体，从而导致格林-巴利综合征（GBS），一种急性多发性神经病。为了确定特定细菌基因是否对于神经节苷脂样结构的生物合成和抗神经节苷脂抗体的诱导至关重要，我们对 GBS 相关菌株和对照菌株中的空肠弯曲菌 LOS 生物合成基因位点进行了表征。我们证明了特定类型的 LOS 生物合成基因座与 GBS 以及神经节苷脂模拟结构的表达相关。 2 个潜在 GBS 标记基因的弯曲杆菌敲除突变体均参与 LOS 唾液酸化，表达不含唾液酸的截短 LOS 结构，显示出与 GBS 患者血清的反应性降低，并且未能在小鼠中诱导抗神经节苷脂抗体反应。据我们所知，我们首次证明特定细菌基因对于诱导抗神经节苷脂抗体至关重要。
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.