孟加拉国与吉兰-巴雷综合征相关的空肠弯曲菌：神经节苷脂模拟和交叉反应性抗体。
Guillain-Barré syndrome-related Campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies.
机构信息
Emerging Diseases and Immunobiology, Centre for Food and Waterborne Diseases, icddr,b, Dhaka, Bangladesh.
出版信息
PLoS One. 2012;7(8):e43976. doi: 10.1371/journal.pone.0043976. Epub 2012 Aug 27.
BACKGROUND
Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.
METHODOLOGY
Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.
PRINCIPLE FINDINGS
IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.
CONCLUSION
Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh.
背景
空肠弯曲菌是格林-巴利综合征（GBS）的主要前驱感染。分子模拟和对空肠弯曲菌脂寡糖（LOS）的交叉反应性免疫应答导致 GBS 的发生，尽管这一机制尚未在发展中国家的患者中得到证实。我们确定了孟加拉国 GBS 患者中 C. jejuni LOS 与神经节苷脂之间的碳水化合物模拟性，以及交叉反应性抗体反应。
方法
通过酶联免疫吸附试验（ELISA）检测 97 例 GBS 患者和 120 例神经和家族对照血清中针对孟加拉国 GBS 患者分离的 C. jejuni LOS 的抗体反应。通过 ELISA 确定 LOS 的交叉反应性。通过质谱法确定与 GBS/MFS 相关的 C. jejuni 菌株的 LOS 外核心结构。
主要发现
与对照组相比（<3%，p<0.001），分别有 56%、58%、14%和 15%的 GBS 患者血清中发现针对 C. jejuni BD-07、BD-39、BD-10 和 BD-67 的 IgG 抗体。针对 GM1 和 GD1a 的单克隆抗体与 C. jejuni 菌株的 LOS 反应强烈（BD-07 和 BD-39）。质谱分析证实 C. jejuni BD-07 和 BD-39 的 LOS 中存在 GM1 和 GD1a 碳水化合物模拟物。BD-10 和 BD-67 表达相同的 LOS 外核心，似乎是一种新的结构，显示 GA2 和 GD3 模拟物。在两名患者（DK-07 和 DK-39）中，高达 90-100%的血清对神经节苷脂的反应被 50µg/ml 来自自身 C. jejuni 分离株的 LOS 抑制。然而，患者 DK-07 产生了抗 GD1a 的免疫应答，而患者 DK-39 产生了抗 GM1 的免疫应答。
结论
C. jejuni LOS 与神经节苷脂之间的碳水化合物模拟性以及交叉反应性血清抗体沉淀了孟加拉国大部分 GBS 病例。
Zotero 插件