Molecular mechanism of Guillain-Barre syndrome after Campylobacter jejuni enteritis : approach from bacterial analysis

格林-巴利综合征（GBS）是一种感染后自身免疫介导的神经病变，是空肠弯曲杆菌肠炎后的一种严重并发症。为了研究发生GBS的细菌危险因素，分析了日本患者分离株的基因型、血清型和脂寡糖（LOS）上的神经节苷脂模拟物。GBS分离株更频繁地分组在LOS生物合成位点A类（72/106 ; 68%）比肠炎分离株（17/103 ; 17%）。A类菌株主要具有基因型cst-II（Thr 51），其负责GM 1-和GD 1a-样LOS的生物合成。事实上，我们发现具有cst-II（Thr 51）的菌株有规律地表达GM 1和GD 1a表位，而具有cst-II（Asn 51）的菌株具有GQ 1b表位。空肠弯曲菌（Thr 51）阳性率较高的患者抗GM 1和抗GD 1a IgG阳性，并有肢体无力。感染空肠弯曲菌（Asn 51）的患者更常出现抗GQ 1b IgG阳性，并出现眼轻瘫和共济失调。GBS患者的cst-Ⅱ基因型以Thr 51为主，而Fisher综合征患者的cst-Ⅱ基因型以Asn 51为主。最近在欧洲报道的GBS分离株中的A类基因座聚类提供了第一个在亚洲和欧洲共有的GBS相关空肠弯曲菌特征。A类基因座似乎与cst-II多态性有关，导致LOS上GM 1和GD 1a样结构合成的促进;因此，增加了产生抗神经节苷脂抗体和发展GBS的风险。空肠弯曲菌的遗传多态性决定了自身抗体反应性和GBS的临床表现，可能是通过修饰宿主模拟分子。

Guillain-Barre syndrome (GBS), a post-infectious autoimmune-mediated neuropathy, is a serious complication after Campylobacter jejuni enteritis. To investigate the bacterial risk factor for developing GBS, genotypes, serotypes and ganglioside-mimics on lipo-oligosaccharide (LOS) were analyzed in the isolates from Japanese patients. GBS isolates more frequently were grouped in LOS biosynthesis locus class A (72/106 ; 68%) than were enteritis isolates (17/103 ; 17%). Class A strains predominantly had genotype cst-II (Thr51), which is responsible for biosynthesis of GM1- and GD1a-like LOSs. Indeed we found that strains with cst-II (Thr51) regularly expressed the GM1 and GD1a epitopes, whereas those with cst-II (Asn51) had the GQ1b epitope. Patients who had C.jejuni (Thr51) more frequently were positive for anti-GM1 and anti-GD1a IgG and had limb weakness. Patients infected with C.jejuni (Asn51) more often were positive for anti-GQ1b IgG and had ophthalmoparesis and ataxia. Predominant cst-II genotype was Thr51 in the isolates from GBS patients, whereas it was Asn51 in those with Fisher syndrome. Class A locus clustering in GBS isolates, recently reported in Europe, provides the first GBS-related C.jejuni characteristic common to Asia and Europe. Class A locus seems to be linked to cst-II polymorphism, resulting in promotion of both GM1- and GD1a-like structure synthesis on LOS ; consequently, increasing the risk of producing anti-ganglioside antibodies and developing GBS. The genetic polymorphism of C.jejuni determines autoantibody reactivity and the clinical presentation of GBS, possibly through modification of the host-mimicking molecule.