Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases
Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases
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DOI：
10.1053/j.gastro.2018.05.030
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发表时间：
2018-09-01
期刊：
影响因子：
29.4
通讯作者：
Wuhrer, Manfred
中科院分区：
文献类型：
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作者：
Clerc, Florent;Novokmet, Mislav;Wuhrer, Manfred
背景与目的：早期发现克罗恩病(CD)和溃疡性结肠炎(UC)或预测患者预后需要生物标志物。糖基化是一种常见而复杂的蛋白质翻译后修饰，影响其结构和活性。我们比较了CD或UC患者和健康人(对照组)的血浆N-糖基化水平。方法：采用连锁特异性唾液酸衍生化技术，对2635例炎症性肠病患者和996例正常对照的血浆总N-糖进行了分析。血浆样本来自意大利的两家医院(发现队列，1989名炎症性肠病患者和570名对照)和美国的一家医疗中心(验证队列，646例炎症性肠病患者和426名对照)。用MassyTools软件从原始数据中提取了63种糖形式，符合我们的相对定量标准。在78个衍生性状中结合了糖组成的共同特征，包括复合型多糖的触角数量以及岩藻糖化、对分、半乳糖化和唾液酸化水平。用线性回归和Logistic回归分析血浆N-血糖与年龄、性别、CD、UC和IBD相关参数如疾病部位、手术和药物、C-反应蛋白水平和沉降率的关系。结果：与对照组相比，IBD患者血浆中大分子糖链的丰度较高，杂合结构和高甘露糖结构的相对丰度降低，岩藻糖化程度降低，半乳糖化程度降低，唾液酸化(α2，3和α2，6连接)增加。我们可以根据较高的二分率、较低的半乳糖化和较高的唾液酸化(α2，3连接)来区分CD患者和UC患者的血浆。糖基化模式与疾病的位置和进展、是否需要更有效的药物以及手术有关。这些结果在一个大型的独立队列中得到了重复。结论：我们进行了高通量分析，以比较患有IBD的个体和没有IBD的个体的血浆总N-糖，并确定与疾病特征和治疗需求相关的模式。这些特征可用于诊断和预测患者对治疗的反应。
BACKGROUND & AIMS: Biomarkers are needed for early detection of Crohn's disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex posttranslational modification of proteins that affects their structure and activity. We compared plasma N-glycosylation profiles between patients with CD or UC and healthy individuals (controls). METHODS: We analyzed the total plasma N-glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique. Plasma samples were acquired from 2 hospitals in Italy (discovery cohort, 1989 patients with inflammatory bowel disease [IBD] and 570 controls) and 1 medical center in the United States (validation cohort, 646 cases of IBD and 426 controls). Sixty-three glycoforms met our criteria for relative quantification and were extracted from the raw data with the software MassyTools. Common features shared by the glycan compositions were combined in 78 derived traits, including the number of antennae of complex-type glycans and levels of fucosylation, bisection, galactosylation, and sialylation. Associations of plasma N-glycomes with age, sex, CD, UC, and IBD-related parameters such as disease location, surgery and medication, level of C-reactive protein, and sedimentation rate were tested by linear and logistic regression. RESULTS: Plasma samples from patients with IBD had a higher abundance of large-size glycans compared with controls, a decreased relative abundance of hybrid and high-mannose structures, lower fucosylation, lower galactosylation, and higher sialylation (alpha 2,3-and alpha 2,6-linked). We could discriminate plasma from patients with CD from that of patients with UC based on higher bisection, lower galactosylation, and higher sialylation (alpha 2,3-linked). Glycosylation patterns were associated with disease location and progression, the need for a more potent medication, and surgery. These results were replicated in a large independent cohort. CONCLUSIONS: We performed high-throughput analysis to compare total plasma N-glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients' responses to treatment.