Odaka M, Yuki N, Yoshino H, Kasama T, Handa S, Irie F, Hirabayashi Y, Suzuki A, Hirata K
Department of Neurology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan.
Ann Neurol. 1998 Jun;43(6):829-34. doi: 10.1002/ana.410430619.
To clarify the pathogenesis of Guillain-Barré syndrome (GBS) after parenteral injections of bovine brain gangliosides, we searched for new molecules in bovine brain gangliosides recognized by sera from GBS patients. Gangliosides fractionated in a Q-Sepharose column were used as the antigens, and the binding of serum IgG or IgM was examined by thin-layer chromatography/immunostaining. Fourteen of 175 serum samples from the patients reacted with the monosialoganglioside fraction 2. In the neutral solvent system, a band in this fraction migrated with N-acetylneuraminic acid-containing GM1 [GM1(NeuAc)], whereas in the alkaline solvent system it migrated slower. This suggested that the band was N-glycolylneuraminic acid-containing GM1 [GM1(NeuGc)]. In both solvent systems, its mobility was almost the same as that of authentic GM1(NeuGc) from mouse liver. Secondary ion mass spectrometry showed that the ganglioside's structure was consistent with that of GM1(NeuGc). IgG anti-GM1(NeuGc) antibodies in sera from the GBS patients were significantly absorbed by GM1(NeuAc), indicative that the anti-GM1(NeuGc) antibodies cross-react with GM1(NeuAc). N-Glycolylneuraminic acid-containing gangliosides are so highly immunogenic in humans that the injection of GM1(NeuGc) could induce the production of IgG anti-GM1(NeuGc) antibody, which cross-reacts with GM1(NeuAc).
为阐明注射牛脑神经节苷脂后吉兰-巴雷综合征(GBS)的发病机制,我们在牛脑神经节苷脂中寻找GBS患者血清所识别的新分子。用Q-琼脂糖柱分离的神经节苷脂作为抗原,通过薄层色谱/免疫染色检测血清IgG或IgM的结合情况。175例患者血清样本中有14例与单唾液酸神经节苷脂组分2发生反应。在中性溶剂系统中,该组分中的一条带与含N-乙酰神经氨酸的GM1 [GM1(NeuAc)]一起迁移,而在碱性溶剂系统中迁移较慢。这表明该条带是含N-羟乙酰神经氨酸的GM1 [GM1(NeuGc)]。在两种溶剂系统中,其迁移率与来自小鼠肝脏的 authentic GM1(NeuGc)几乎相同。二次离子质谱显示该神经节苷脂的结构与GM1(NeuGc)一致。GBS患者血清中的IgG抗GM1(NeuGc)抗体被GM1(NeuAc)显著吸收,表明抗GM1(NeuGc)抗体与GM1(NeuAc)发生交叉反应。含N-羟乙酰神经氨酸的神经节苷脂在人类中具有高度免疫原性,以至于注射GM1(NeuGc)可诱导产生与GM1(NeuAc)发生交叉反应的IgG抗GM1(NeuGc)抗体。