空肠弯曲菌诱导外周神经免疫损伤的关键抗原研究

空肠弯曲菌诱导外周神经免疫损伤的关键抗原研究
王晓红;束晓梅;杨冰竹
【期刊名称】《临床儿科杂志》
【年(卷),期】2011(29)1
【摘要】Objective To explore whether lipo-oligosaccharide ( LOS) in Campylobacter jejuni ( CJ) is a critical antigen to induce damage of peripheral nerve, and to provide an immunology experimental evidence on CJ infection induced Guillain-Barr(e) syndromes ( GBS ) for the presumption of molecular mimicry.Methods A comparing study was carried out using the CJ parent strain ( with LOS and ganglioside-like epitopes ) and its direct waaF gene knockout mutant ( waaF mutant without LOS and ganglioside-like epitopes ).A total of 26 Japanese white rabbits were randomly divided into three groups, parental strain group (n = 10), waaF mutant group (n = 10), and control group (n = 6).Three groups were immunized with Freund's adjuvant ( FA) plus parental strains of CJ HB9313, waaF mutants, and saline respectively.Enzyme linked immunosorbent assay ( ELISA ) was employed to detect serum anti ganglioside GMl-IgG antibodies.At 8th week after immunization, the animals were sacrificed.The sciatic nerves were separated.The expression of GMl, GMl-IgG antibody and C3c complement deposited on the sciatic nerves were detected by direct immunofluorescence.The pathologic changes were detected in a teased-fiber study.Results The ELISA results
showed that the parental strain group had significantly higher serum GMl-IgG antibody titers at 2 weeks, which were further raised at 4 weeks, peaked at 6 weeks, and sustained at 8 weeks.The serum GMl-IgG antibodies had raised 4 times more than before immunization at 6 weeks.However, both waaF mutant group and control group displayed no raised levels of serum GMl-IgG antibody.Immunofluorescence results showed that the nodes of Ranvier and the paranodal myelin with fluorescein-labelled cholera toxin B subunit ( ligand of ganglioside GMl ) were positively stained in three groups.Deposition of GMl-IgG antibody and complement C3c at the nodes of Ranvier of sciatic nerves were observed in 4 rabbits from parental strain group.No such changes were observed in waaF mutant group and control group.The results of teased-fiber study on sciatic nerves showed that the incidence of pathologic abnormalities of teased-fibers from the mutants group was 4.9％, significantly lower than 16％ from the parental strains group ( P ＜
0.01 ).For parental strains group, the predominant abnormality of teased-fibers was axonal degeneration.Conclusions The results confirmed that the ganglioside-like epitope in LOS of CJ is a critical antigen to induce GMl-IgG antibody.Anti-ganglioside antibodies can bind peripheral nerve nodes of Ranvier, activate the complement cascade, and induce pathological changes with axonal degeneration.This supports the molecular mimicry theory as a pathogenesis in the axonal Guillain-Barre syndrome induced by CJ infection.%目的探索空肠弯曲菌(CJ)诱导周围神经损伤的关键抗原结构.为CJ 诱发Guillain-Barré综合征的分子模拟理论提供免疫学证据.方法利用CJ亲代株
(含脂寡糖及神经节苷脂结构)及waaF变异株(缺失脂寡檐及神经节苷脂结构)作为抗原,进行对照研究.将26只日本大耳兔随机分为CJ亲代株组(10只)、waaF变异株组(10只)、对照组(6只),分别用亲代株CJ、waaF变异株及免疫佐剂,对3组动物进行全身免疫.ELISA动态检测3组动物血清中神经节苷脂GM1-IgG抗体变化;于8周末,取动物坐骨神经进行免疫荧光检查,包括神经节苷脂(GM1)表达、GM1-IgG抗体及补体C3c的检查;对动物坐骨神经进行单纤维分离,检查病理形态学改变.结果①亲代株组动物免疫后2周,血清中抗GM1-IgG抗体滴度增高,4周进一步增高,6周达高峰,高于免疫前的4倍,持续到8周末见明显下降;waaF变异株和对照组免疫后未见抗GM1-IgG抗体增高.②免疫荧光检查显示3组动物坐骨神经均见GM1特异性配体-霍乱毒素B亚单位(CTB)在髓鞘及Ranvier结处不同程度染色.亲代株组4只动物坐骨神经Ranvier结处可见GM1-IgG抗体沉积及补体C3c染色;waaF变异株组均未见GM1抗体及补体C3c染色.③亲代株组单纤维病变率为16.0%(320/2 000),变异株组的病变率仅为4.9%(98/2 000),两者差异有统计学意义(P<0.01),亲代株所致病理变化主要为轴索变性.结论 CJ外膜脂寡糖上神经节苷脂结构是诱导动物产生GM1抗体的关键结构,GM1-IgG抗体可沉积在周围神经Ranvier结,激活补体瀑布反应发生,诱发周围神经轴索型病理异常,支持CJ感染相关轴索型GBS的分子模拟发病理论.
【总页数】5页(P68-72)
【作者】王晓红;束晓梅;杨冰竹
【作者单位】遵义医学院附属医院儿科,贵州遵义,563003;遵义医学院附属医院儿科,贵州遵义,563003;遵义医学院附属医院儿科,贵州遵义,563003
【正文语种】中文
【中图分类】Q95-3
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