Ganglioside mimicry as a cause of Guillain-Barre syndrome
Ganglioside mimicry as a cause of Guillain-Barre syndrome
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DOI：
10.1097/01.wco.0000174604.42272.2d
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发表时间：
2005-10-01
影响因子：
4.8
通讯作者：
Odaka, M
中科院分区：
文献类型：
--
作者：
Yuki, N;Odaka, M
综述目的空肠弯曲菌是吉兰-巴利综合征轴突变异型、急性运动轴突神经病中最常见的既往感染病原体，抗 GM1 或抗 GD1 IgG 抗体也与急性运动轴突神经病相关。在人 GM1 神经节苷脂和从急性运动轴突神经病患者中分离的空肠弯曲菌的脂寡糖之间发现了分子模拟。吉兰-巴利综合征的研究取得了进展，特别是空肠弯曲菌肠炎引起的急性运动轴索神经病变。最近的研究结果表明，空肠弯曲菌低聚脂糖和GM1对家兔致敏，诱导产生抗GM1 IgG抗体，并随后发生急性弛缓性麻痹。兔周围神经的病理变化与人类急性运动轴突神经病的病理变化相同。这些发现提供了确凿的证据，表明分子拟态是人类自身免疫性疾病的原因。神经节苷脂样脂寡糖由唾液酸转移酶 Cst-II、N-乙酰半乳糖胺基转移酶 CgtA 和半乳糖基转移酶 CgtB 合成。这些基因的同时存在与格林-巴利综合征相关的空肠弯曲菌菌株之间存在密切关联。参与脂寡糖唾液酸化的空肠弯曲菌基因的敲除突变体与来自吉兰-巴利综合征患者的抗GM1血清的反应性降低，并且不会在小鼠中诱导抗GD1a IgG抗体反应。脂寡糖生物合成基因似乎对于诱导抗 GM1 或抗 GD1 IgG 抗体以及随后发生急性运动轴突神经病至关重要。 总结碳水化合物拟态导致自身免疫性疾病的概念为解决其他免疫介导疾病的发病机制提供了线索。
Purpose of review Campylobacter jejuni is the most frequent agent of antecedent infection in an axonal variant of Guillain-Barre syndrome, acute motor axonal neuropathy, and anti-GM1 or anti-GD1 a lgG antibody is also associated with acute motor axonal neuropathy. Molecular mimicry has been found between human GM1 ganglioside and the lipo-oligosaccharicle of C. jejuni isolated from an acute motor axonal neuropathy patient. Progress has been made in Guillain-Barre syndrome research, especially on acute motor axonal neuropathy subsequent to C. jejuni enteritis.Recent findings Sensitization of rabbits with C. jejuni lipo-oligosaccharide, as well as GM1, induced the production of anti-GM1 lgG antibody, and the subsequent development of acute flaccid paralysis. Pathological changes in rabbit peripheral nerves were identical to those seen in human acute motor axonal neuropathy. These findings provide conclusive evidence that molecular mimicry is a cause of human autoimmune disease. Ganglioside-like lipo-oligosaccharicle is synthesized by sialyltransferase Cst-II, N-acetylgalactosaminyl-transferase CgtA, and galactosyltransferase CgtB. There is a strong association between the simultaneous presence of these genes and Guillain - Barre syndrome-associated C. jejuni strains. Knockout mutants of C. jejuni genes involved in lipo-oligosaccharicle sialylation had reduced reactivity with anti-GM1 sera from Guillain-Barre syndrome patients, and did not induce an anti-GD1 a IgG antibody response in mice. Lipo-oligosaccharide biosynthesis genes appear to be essential for the induction of anti-GM1 or anti-GD1 a IgG antibody and the subsequent development of acute motor axonal neuropathy.Summary The concept that carbohydrate mimicry causes autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.