Antecedent infections in Fisher syndrome - A common pathogenesis of molecular mimicry
Antecedent infections in Fisher syndrome - A common pathogenesis of molecular mimicry
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DOI：
10.1212/01.wnl.0000160399.08456.7c
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发表时间：
2005-05-10
期刊：
影响因子：
9.9
通讯作者：
Yuki, N
中科院分区：
文献类型：
--
作者：
Koga, M;Gilbert, M;Yuki, N
目的：探讨Fisher综合征（FS）患者抗GQ1b自身抗体的产生机制。研究方法：作者在73例FS患者和73例性别和年龄匹配的医院对照（HC）中对5种既往感染（空肠弯曲菌、巨细胞病毒、EB病毒、肺炎支原体和流感嗜血杆菌）进行了前瞻性病例对照血清学研究。FS患者的血清学证据显示C。jejuni（21%）和H.流感病毒感染（8%）明显多于HC。在49例（67%）FS患者中未发现5种病原体。大多数FS患者感染C. jejuni或H.流感。质谱分析鉴定出一个C.空肠菌株（CF93 - 6）携带从FS患者分离的GT1a样脂寡糖（LOS）。用GT1a样LOS免疫缺乏复杂神经节苷脂的敲除小鼠，产生与GQ1b和GT1a反应的IgG类单克隆抗体（mAb）。薄层层析结合免疫染色显示抗GQ1b mAb与C.空肠LOS（50%的20 FS相关菌株）比格林-巴利综合征（GBS）相关（7%的70）或肠炎相关（20%的65）菌株更常见。抗GM1和抗GD1a mAb也与来自某些FS相关菌株的LOS反应（均为20%），但在GBS相关菌株中结合频率较高（74%和57%）。GQ1b表位在10例FS相关H中的4例（40%）中检测到。流感病毒株，但没有在菌株与GBS（n = 4）和简单的呼吸道感染（n = 10）的患者。结论：C. jejuni和H.流感与Fisher综合征（FS）的发展有关，并且抗GQ1b自身抗体的产生由这些细菌上的GQ1b模拟脂寡糖介导。在大多数FS患者中，病因尚不清楚。
Objective: To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS). Methods: The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barre syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10). Conclusions: C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.