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An evaluation of anti-VacA antibody and its target molecules in the cerebrospinal fluid of patients with demyelinating form of Guillain-Barre syndrome.

格林-巴利综合征脱髓鞘患者脑脊液中抗 VacA 抗体及其靶分子的评估。

基本信息

批准号：
15500242
负责人：
CHIBA Susumu
金额：
$ 1.92万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Immunological studyIn order to detect antibodies against recombinant vacuolating cytotoxin (r-VacA) of Helicobacter pylori (H.pylori) in the cerebrospinal fluid (CSF) from patients with Guillain-Barre syndrome (GBS). The CSF samples from 13 patients with GBS (electrophysiologically classified as 8 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 4 acute motor axonal neuropathy (AMAN), and 1 unexcitable) and 8 disease control patients were studied. The r-VacA protein was separated by SDS-PAGE and Western blot analysis was carried out. Six of the 13 GBS patients had a specific IgG antibody against VacA of H.pylori, which was confirmed by absorption experiments using r-VacA. Every patient with positive CSF anti-r-VacA antibody had AIDP. The sequence homology between VacA and human (Na^++K^+)-ATPase α subunit has been outlined. Our findings lead to the possible hypothesis that anti-VacA antibodies involve ion channels in abaxonal Schwann cell plasmalemma resulting in demyeli … More nation in some patients with GBS.Histochemical evaluationTo identify the target molecules of anti-VacA-antibody (A-VacA-Ab) in the human ventral nerve roots, the immunohistochemical examination was carried out. A-VacA-Ab obtained from rabbits was prepared by immunization of the native VacA purified by the culture media of H.pylori. Cervical ventral nerve roots were obtained from patients with no known neurologic disorders within two hours after death. Both DAB and FITC procedures were employed. Disseminated spotty stainings were observed in cross sections. In longitudinal sections, string-like immunostainings were also seen both by DAB and FITC procedures. These were localized within the nerve fibers. Consequently, the target epitopes of A-VacA-Ab were thought to be present in the myelin components of the nerve roots. These results indicate that the target molecules of A-VacA-Ab in the cerebrospinal fluid obtained from patients with GBS are probably associated with some components of the peripheral nerve myelin. A-VacA-Ab may play an important role in the immune responses of patients with the demyelinating form of GBS. Less

免疫学研究检测格林-巴利综合征（GBS）患者脑脊液（CSF）中幽门螺杆菌（H.pylori）重组空泡毒素（r-VacA）抗体。研究了13例GBS患者（电生理分类为8例急性炎性脱髓鞘性多神经根神经病（AIDP），4例急性运动轴突神经病（AMAN）和1例不兴奋性）和8例疾病对照患者的CSF样本。经SDS-PAGE分离r-VacA蛋白，并进行Western blot分析。13例GBS患者中有6例具有针对幽门螺杆菌VacA的特异性IgG抗体，这通过使用r-VacA的吸收实验来证实。脑脊液抗r-VacA抗体阳性者均为AIDP。VacA与人（Na^++K^+）-ATP酶α亚基之间的序列同源性已被概述。我们的研究结果导致了一种可能的假设，即抗VacA抗体参与了离轴雪旺细胞质膜的离子通道，导致了脱髓鞘。 ...更多信息组织化学评价为确定抗VacA抗体（A-VacA-Ab）在人腹神经根中的靶分子，进行了免疫组织化学检测。以经幽门螺杆菌（H. pylori）培养液纯化的天然VacA免疫家兔制备A-VacA-Ab。颈前神经根取自死亡后两小时内没有已知神经系统疾病的患者。采用DAB和FITC程序。在横截面中观察到弥散性点状染色。在纵向切片中，通过DAB和FITC程序也可以看到线状免疫染色。它们位于神经纤维中。因此，A-VacA-Ab的靶表位被认为存在于神经根的髓鞘组分中。这些结果表明GBS患者脑脊液中A-VacA-Ab的靶分子可能与周围神经髓鞘的某些成分有关。A-VacA-Ab可能在脱髓鞘型GBS患者的免疫应答中起重要作用。少