Glycosylation is important for biological functions of proteins and greatly affected by diseases. Exploring the glycosylation profile of the protein-specific glycosylation and/or the site-specific glycosylation may help understand disease etiology, differentiate diseases and ultimately develop therapeutics. Patients with multiple sclerosis (MS) and patients with neuromyelitis optica spectrum disorder (NMOSD) are sometimes difficult to differentiate due to the similarity in their clinical symptoms. The disease-related glycosylation profiles of MS and NMOSD have not yet been well studied. Here, we analyzed site-specific glycan profiles of serum proteins of these patients by using a recently developed mass spectrometry technique. A total of 286 glycopeptides from 49 serum glycoproteins were quantified and compared between healthy controls (n = 6), remitting MS (n = 45) and remitting NMOSD (n = 23) patients. Significant differences in the levels of site-specific N-glycans on inflammation-associated components [IgM, IgG1, IgG2, complement components 8b (CO8B) and attractin], central nerve system-damage-related serum proteins [apolipoprotein D (APOD), alpha-1-antitrypsin, plasma kallikrein and ADAMTS-like protein 3] were observed among three study groups. We furthered demonstrated that site-specific N-glycans on APOD on site 98, CO8B on sites 243 and 553 are potential markers to differentiate MS from NMOSD with an area under receiver operating curve value > 0.75. All these observations indicate that remitting MS or NMOSD patients possess a unique disease-associated glyco-signature in their serum proteins. We conclude that monitoring one’s serum protein glycan profile using this high-throughput analysis may provide an additional diagnostic criterion for differentiating diseases, monitoring disease status and estimating response-to-treatment effect.

中文翻译：

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多发性硬化症或视神经脊髓炎谱系障碍患者血清蛋白的位点特异性聚糖谱分析——一项初步研究

糖基化对蛋白质的生物学功能很重要，并且受疾病的影响很大。探索蛋白质特异性糖基化和/或位点特异性糖基化的糖基化谱可能有助于了解疾病病因、区分疾病并最终开发治疗方法。多发性硬化症 (MS) 患者和视神经脊髓炎谱系障碍 (NMOSD) 患者有时由于临床症状相似而难以区分。MS 和 NMOSD 的疾病相关糖基化谱尚未得到很好的研究。在这里，我们使用最近开发的质谱技术分析了这些患者血清蛋白的位点特异性聚糖谱。对来自 49 种血清糖蛋白的总共 286 种糖肽进行了量化，并在健康对照之间进行了比较（n  = 6)、缓解 MS ( n  = 45) 和缓解 NMOSD ( n  = 23) 患者。炎症相关成分 [IgM、IgG1、IgG2、补体成分 8b ( CO8B ) 和吸引素]、中枢神经系统损伤相关血清蛋白 [载脂蛋白 D (APOD) 、在三个研究组中观察到 α-1-抗胰蛋白酶、血浆激肽释放酶和 ADAMTS 样蛋白 3]。我们进一步证明了特定于站点的N位点 98 上 APOD 上的 -聚糖、位点 243 和 553 上的 CO8B 是区分 MS 与 NMOSD 的潜在标志物，其接受者操作曲线下面积值 > 0.75。所有这些观察结果表明，缓解 MS 或 NMOSD 患者的血清蛋白中具有独特的疾病相关糖特征。我们得出结论，使用这种高通量分析监测一个人的血清蛋白聚糖谱可能为区分疾病、监测疾病状态和估计对治疗效果的反应提供额外的诊断标准。