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Investigation on the significance of the epitope formed by ganglioside and phospholipid in neuroimmunological diseases

神经节苷脂与磷脂形成的表位在神经免疫疾病中的意义研究

基本信息

批准号：
14570581
负责人：
KUSUNOKI Susumu
金额：
$ 2.18万
依托单位：
Kinki University (2003)The University of Tokyo (2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Antiganglioside antibodies are useful diagnostic markers of autoimmune neuropathies. They may be involved in the pathogenetic mechanisms as well. Gangliosides in the cell membrare are surrounded by phospholipids. We investigated serum antibody activities against a mixture of a ganglioside and a phospholipid. The reactivities of the anti-GM1 IgG antibodies in Guillain-Barre syndrome(GBS) were enhanced by the use of a mixture antigen of GM1 and such a phospholipid as PA,PS and PI. Such an enhancement was not seen for the anti-GQ1b IgG antibodies in Miller Fisher syndrome. The reactivates of both of those antibodies were reduced by the addition of SM. The reactivities of the anti-GM1 IgM antibodies in autoimmune neuropathies such as GBS, chronic inflammatory demyelinating polyradiculoneuropathy, and multifocal motor neuropathy were not enhanced by the addition of such a phospholiid as PA,PS and PI to the antigen mixture, while those were reduced by the addition of SM. The effect of SM that decreases the reactivities of the antiganglioside antibodies in autoimmune neuropathies may be the reason why an antiganglioside antibody does not cause ubiquitous damage on the neurological system but affects only the place where the ganglioside is densely localized. The binding activities of the anti-GalNAc-GD1a IgG antibodies were enhanced by the addition of PA to die antigen mixture. This resembles the results on the anti-GM1 IgG antibodies as described above. This may be due to the fact that both of the antibodies are associated with die preceding Campylobacter jejuni infection. Our results suggest that we should pay more attention to the effect by the phospholipids when we consider the role of the antiganglioside antibodies in the pathogenetic mechanisms. Similar investigation is needed on the serum antibodies in the neuroimmunological diseases other than autoimmune neuropathies.

抗神经节苷脂抗体是自身免疫性神经病的有用诊断标志物。它们可能也参与了发病机制。细胞膜中的神经节苷脂被磷脂包围。我们研究了血清抗体对神经节苷脂和磷脂的混合物的活动。用GM_1与PA、PS、PI等磷脂混合抗原，可增强格林-巴利综合征（GBS）患者抗GM_1 IgG抗体的反应性。这种增强在米勒费舍尔综合征中的抗GQ 1b IgG抗体中未观察到。这两种抗体的再活化通过添加SM而减少。抗GM 1 IgM抗体在自身免疫性神经病如GBS、慢性炎性脱髓鞘性多发性神经根神经病和多灶性运动神经病中的反应性不通过向抗原混合物中添加磷脂如PA、PS和PI而增强，而通过添加SM而降低。SM降低抗神经节苷脂抗体在自身免疫性神经病中的反应性的作用可能是抗神经节苷脂抗体不会对神经系统造成普遍损害而仅影响神经节苷脂密集定位的地方的原因。通过向抗原混合物中加入PA增强抗GalNAc-GD 1a IgG抗体的结合活性。这类似于上述抗GM 1 IgG抗体的结果。这可能是由于这两种抗体都与先前的空肠弯曲菌感染有关。我们的研究结果提示，当我们考虑抗神经节苷脂抗体在发病机制中的作用时，我们应该更多地关注磷脂的作用。除自身免疫性神经病外，其他神经免疫性疾病的血清抗体也需要进行类似的研究。