Yuki N, Taki T, Inagaki F, Kasama T, Takahashi M, Saito K, Handa S, Miyatake T
Department of Neurology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
J Exp Med. 1993 Nov 1;178(5):1771-5. doi: 10.1084/jem.178.5.1771.
There is a strong association between Guillain-Barré syndrome (GBS) and Penner's serotype 19 (PEN 19) of Campylobacter jejuni. Sera from patients with GBS after C. jejuni infection have autoantibodies to GM1 ganglioside in the acute phase of the illness. Our previous work has suggested that GBS results from an immune response to cross-reactive antigen between lipopolysaccharide (LPS) of the Gram-negative bacterium and membrane components of peripheral nerves. To clarify the pathogenesis of GBS, we have investigated whether GM1-oligosaccharide structure is present in the LPS of C. jejuni (PEN 19) that was isolated from a GBS patient. After extraction of the LPS, the LPS showing the binding activity of cholera toxin, that specifically recognizes the GM1-oligosaccharide was purified by a silica bead column chromatography. Gas-liquid chromatography-mass spectrometric analysis has shown that the purified LPS contained Gal, GalNAc, and NeuAc, which are sugar components of GM1 ganglioside. 1H NMR methods [Carr-Purcell-Meiboom-Gill (CPMG), total correlation spectroscopy (TOCSY), and nuclear Overhauser effect spectroscopy (NOESY)] have revealed that the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] protrude from the LPS core. This terminal structure [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] is identical to the terminal tetrasaccharide of the GM1 ganglioside. This is the first study to demonstrate the existence of molecular mimicry between nerve tissue and the infectious agent that elicits GBS.
吉兰 - 巴雷综合征（GBS）与空肠弯曲菌的彭纳19型血清型（PEN 19）之间存在密切关联。空肠弯曲菌感染后GBS患者的血清在疾病急性期具有针对GM1神经节苷脂的自身抗体。我们之前的研究表明，GBS是由对革兰氏阴性菌脂多糖（LPS）与外周神经膜成分之间交叉反应性抗原的免疫反应引起的。为了阐明GBS的发病机制，我们研究了从一名GBS患者分离出的空肠弯曲菌（PEN 19）的LPS中是否存在GM1 - 寡糖结构。提取LPS后，通过硅胶珠柱色谱法纯化显示霍乱毒素结合活性（霍乱毒素特异性识别GM1 - 寡糖）的LPS。气 - 液色谱 - 质谱分析表明，纯化的LPS含有GM1神经节苷脂的糖成分半乳糖（Gal）、N - 乙酰半乳糖胺（GalNAc）和唾液酸（NeuAc）。1H核磁共振方法[卡 - 普 - 梅 - 吉尔序列（CPMG）、全相关谱（TOCSY）和核Overhauser效应谱（NOESY）]显示，寡糖结构[β - 半乳糖1 - 3 N - 乙酰半乳糖胺β1 - 4（α - 唾液酸2 - 3）半乳糖β]从LPS核心突出。这种末端结构[β - 半乳糖1 - 3 N - 乙酰半乳糖胺β1 - 4（α - 唾液酸2 - 3）半乳糖β]与GM1神经节苷脂的末端四糖相同。这是首次证明引发GBS的感染因子与神经组织之间存在分子模拟的研究。
