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.

食用煮熟的小龙虾可能会导致哈夫病（HD），这种病被认为是由一种不明毒素引起的，尽管其病因仍不清楚。HD 中 N-糖组的分析将有助于破译该疾病的潜在分子机制，而 HD 相关的糖基化尚未被探索过。在此，我们收集了 2019 年至 2020 年间来自武汉疾病预防控制中心的 90 份 HD 患者和健康对照的血清样本。HD 中血清和血清源性免疫球蛋白 G (IgG) 的 N 糖组谱通过以下方法进行表征：基于高通量的正交质谱分析。据观察，HD 与总血清糖蛋白的核心岩藻糖基化和单半乳糖基化增加有关。研究发现血清 IgG 水平可以作为 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。有趣的是，IgG2 或 IgG3/4 唾液酸化和半乳糖基化的改变与 HD 的临床标志物密切相关。我们的研究揭示了差异性 IgG N-糖基化与 HD 的关联，为这种罕见疾病的病因学提供了新的见解。IgG2 或 IgG3/4 唾液酸化和半乳糖基化的改变与 HD 的临床标志物密切相关。我们的研究揭示了差异性 IgG N-糖基化与 HD 的关联，为这种罕见疾病的病因学提供了新的见解。IgG2 或 IgG3/4 唾液酸化和半乳糖基化的改变与 HD 的临床标志物密切相关。我们的研究揭示了差异性 IgG N-糖基化与 HD 的关联，为这种罕见疾病的病因学提供了新的见解。