Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential.
Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential.
复制标题
多发性硬化症中糖基化改变显示出增加的促炎潜力。
DOI：
10.3390/biomedicines8100410
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发表时间：
2020-10-13
期刊：
影响因子：
4.7
通讯作者：
Štambuk T
中科院分区：
文献类型：
--
作者：
Cvetko A;Kifer D;Gornik O;Klarić L;Visser E;Lauc G;Wilson JF;Štambuk T
多发性硬化（MS）是一种影响中枢神经系统（CNS）的炎性自身免疫性疾病，病因尚未明确。以前的研究已经暗示N-糖基化，一种高度调节的酶促连接的复杂糖的目标蛋白质，在MS的发病机制。我们研究了MS中总血浆蛋白质组和IgG N-糖基化的个体变异。在83例MS病例和88例年龄和性别匹配的对照中，对血浆蛋白和IgG N-聚糖进行了色谱分析和定量。比较MS病例和对照之间的糖基化特征水平，发现核心岩藻糖基化（p = 6.96 × 10−3）和高甘露糖结构丰度（p = 1.48 × 10−2）是最显著改变的IgG糖基化特征。对于触角岩藻糖基化、三唾液酸化和四唾液酸化、三半乳糖基化和四半乳糖基化、高分支N-聚糖，观察到血浆蛋白N-糖组组成的显著变化（p值范围为1.66 × 10−2-4.28 × 10−2）。通过ROC曲线分析检查N-聚糖的分类性能，得到总血浆N-糖组的AUC为0.852，IgG N-糖组预测模型的AUC为0.798。我们的研究结果表明，MS中蛋白质糖基化的多个方面发生了改变，显示出增加的促炎潜力。N-聚糖改变在疾病状态的分类中显示出实质性价值，尽管如此，还需要进行额外的研究来探索其在MS发展中的确切作用和作为生物标志物的效用。
Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10−3) and abundance of high-mannose structures (p = 1.48 × 10−2) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10−2–4.28 × 10−2). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers.
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影响因子：
4.6
作者：
Sakae Y;Satoh T;Yagi H;Yanaka S;Yamaguchi T;Isoda Y;Iida S;Okamoto Y;Kato K
通讯作者：
Kato K
DOI：
10.3233/wor-152200
发表时间：
2015-01-01
影响因子：
2.3
作者：
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通讯作者：
Rumrill, Phillip D.
影响因子：
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作者：
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影响因子：
2
作者：
Sarrats, Ariadna;Saldova, Radka;Peracaula, Rosa
通讯作者：
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影响因子：
9.3
作者：
Olesen, M. N.;Soelberg, K.;Asgari, N.
通讯作者：
Asgari, N.