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基于正交质谱的N-糖组谱揭示哈夫病潜在病原学
Si Liu, Yuanyuan Liu, Jiajing Lin, Bi-Feng Liu, Zhenyu He, Xiaomin Wu, Xin Liu
工程（英文） ›› 2021, Vol. 26 ›› Issue (7) : 63-73.
PDF(1930 KB)
PDF(1930 KB)
基于正交质谱的N-糖组谱揭示哈夫病潜在病原学
Novel Insight into the Etiology of Haff Disease by Mapping the N-Glycome with Orthogonal Mass Spectrometry
食用煮熟的小龙虾可能导致哈夫病（HD），该病被认为是由不明毒素引起的，而病因尚不清楚。N-糖组的剖析将有助于破译疾病的分子机制，而HD相关的糖基化从未被探索过。2019—2020 年，本研究团队招募了来自武汉市疾病预防控制中心的90 份HD患者和对照组血清样本。本文中，采用基于高通量的正交质谱对HD中血清和血清衍生的免疫球蛋白G（IgG） N-糖组谱进行了表征。数据显示，HD与总血清糖蛋白的核心岩藻糖基化和单半乳糖基化升高有关。血清IgG 水平是诊断HD患者的良好指标。此外，IgG的差异半乳糖基化和唾液酸化与HD密切相关。值得注意的是，IgG1 和IgG2 的半乳糖基化和唾液酸化的变化具有亚类特异性。有意义的是，IgG2 或IgG3/4 的唾液酸化和半乳糖基化改变与HD的临床标志物密切相关。本研究揭示了差异化IgG N-糖基化与HD的关联，为这种罕见疾病的病因提供了新的见解。
Consumption of boiled crayfish may lead to Haff disease (HD), which is considered to result from an unidentified toxin, although the etiology is still obscure. Profiling of the N-glycome in HD would assist in deciphering the underlying molecular mechanism of the disease, whereas HD-associated glycosylation has never been explored. Herein, we enrolled 90 serum samples with HD patients and healthy controls from the Wuhan Center for Disease Control & Prevention between 2019 and 2020. N-glycome profiles of both serum and serum-derived immunoglobulin G (IgG) in HD were characterized by means of high-throughput-based orthogonal mass spectrometry. It was observed that HD is associated with an increase in the core fucosylation and mono-galactosylation of total serum glycoproteins. The serum level of IgG was found to serve as a good indicator for HD patients. In addition, differential galactosylation and sialylation of IgG were strongly correlated with HD. It was notable that the changes in the galactosylation and sialylation of IgG1 and IgG2 were subclass specific. Interestingly, altered sialylation and galactosylation of IgG2 or IgG3/4 strongly correlated with clinical markers for HD. Our study reveals the association of differential IgG N-glycosylation with HD, providing new insight into the etiology of this rare disease.
哈夫病 / 全血清 / IgG抗体 / N-糖基化 / 疾病病原学
Haff disease / Serum / Immunoglobulin G / Glycosylation / Disease pathogenesis
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