Complex of GM1- and GD1a-like lipo-oligosaccharide mimics GM1b, inducing anti-GM1b antibodies.

Complex of GM1- and GD1a-like lipo-oligosaccharide mimics GM1b, inducing anti-GM1b antibodies.
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GM1和GD1A样脂肪含糖的复合物模拟GM1B,诱导抗GM1B抗体。

DOI:
10.1371/journal.pone.0124004
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Yuki N
Yuki N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Koga M;Gilbert M;Li J;Yuki N

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空肠弯曲杆菌脂寡糖 (LOS) 与人神经节苷脂 GM1 和 GD1a 之间的分子模拟诱导抗 GM1 和抗 GD1a 抗体的产生,以及格林-巴利综合征的发生。两种不同神经节苷脂的复合物形成新的分子形状,能够增强抗神经节苷脂抗体的识别。测试空肠弯曲菌的 GM1 样和 GD1a 样 LOS 复合物诱导格林-巴利综合征患者产生抗 GM1b 抗体的假设。质谱分析确定了 LOS 外核结构,并用该结构对小鼠进行免疫。在分离出空肠弯曲菌 LOS 的格林-巴利综合征患者的血清中测试了针对单一神经节苷脂和复合神经节苷脂的 IgG 抗体。来自 GBS 患者的两个分离株具有抗 GM1b 抗体,但既没有抗 GM1 也没有抗 GD1a 抗体,表达 GM1 样和 GD1a 样 LOS,但不表达 GM1b 样 LOS。在一只用带有 GM1 样和 GD1a 样 LOS 的空肠弯曲菌免疫的小鼠中诱导了抗 GM1b 抗体。 20 名患者的血清含有针对 GM1 和 GD1a 复合物的抗体,所有抗体都带有抗 GM1b 反应性。其中 5 份血清既不含有抗 GM1 抗体,也不含有抗 GD1a 抗体。复合物的 IgG 抗体被 GM1b 吸收,但 GM1 和 GD1a 均不吸收。 GM1 样和 GD1a 样 LOS 形成 GM1b 表位,诱导空肠弯曲菌肠炎后格林-巴利综合征患者产生抗 GM1b 抗体。在这里,我们提出了一种新的范例,即两种不同结构的复合物形成一种新的分子拟态,诱导自身抗体的产生。
Molecular mimicry between Campylobacter jejuni lipo-oligosaccharides (LOSs) and human gangliosides GM1 and GD1a induces the production of anti-GM1 and anti-GD1a antibodies, and the development of Guillain-Barré syndrome. Complexes of two different gangliosides form new molecular shapes capable of enhancing recognition by anti-ganglioside antibodies. To test the hypothesis that the complex of GM1-like and GD1a-like LOSs of C. jejuni induces the development of anti-GM1b antibodies in Guillain-Barré syndrome patients. Mass spectrometry analysis determined the LOS outer core structures, with which mice were immunized. IgG antibodies to single gangliosides and complex of gangliosides were tested in sera from Guillain-Barré syndrome patients from whom C. jejuni LOS had been isolated. Two isolates from GBS patients who had anti-GM1b antibodies, but neither anti-GM1 nor -GD1a antibodies, expressed both GM1-like and GD1a-like LOSs, but not GM1b-like LOS. Anti-GM1b antibodies were induced in one of the mice immunized with the C. jejuni bearing GM1-like and GD1a-like LOS. Sera from 20 patients had antibodies to the complex of GM1 and GD1a, all of which carried anti-GM1b reactivity. Five of these sera harbored neither anti-GM1 nor anti-GD1a antibodies. IgG antibodies to the complex were absorbed by GM1b, but by neither GM1 nor GD1a. GM1-like and GD1a-like LOSs form a GM1b epitope, inducing the development of anti-GM1b antibodies in patients with Guillain-Barré syndrome subsequent to C. jejuni enteritis. Here, we present a new paradigm that the complex of two different structures forms a new molecular mimicry, inducing the production of autoantibodies.
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