血漿N-聚糖的特點與炎症性腸病的特點相關聯

最新 05-31

今天與大家一起來學習於2018年5月21日發表在Gastroenterology上的一篇文章：PlasmaN-Glycan Signatures Associate With Features of Inflammatory Bowel Diseases《血漿N-聚糖的特點與炎症性腸病的特點相關聯》。

下面對這篇文章進行簡要介紹：

BACKGROUND & AIMS:

Biomarkersare needed for early detection of Crohn"s disease (CD) and ulcerative colitis(UC) or to predict patient outcomes. Glycosylation is a common and complexpost-translational modification of proteins that affects their structure andactivity. We compared plasma N-glycosylation profiles between patients with CDor UC and healthy individuals (controls).

背景和目的：

早期發現克羅恩病（CD）和潰瘍性結腸炎（UC）或者預測患者治療結果需要使用生物標誌物。糖基化是一種常見且複雜的蛋白質轉錄後修飾，其會影響蛋白質的結構和活性。我們對比了CD或UC患者與健康人（對照組）之間的血漿N-糖基化譜。

METHODS:

We analyzed thetotal plasma N-glycomes of 2635 patients with inflammatory bowel diseases and996 controls by mass spectrometry with a linkage-specific sialic acidderivatization technique. Plasma samples were acquired from 2 hospitals inItaly (discovery cohort, 1989 patients with IBD and 570 controls) and 1 medicalcenter in the United States (validation cohort, 646 cases of IBD and 426controls). Sixty-three glycoforms met our criteria for relative quantificationand were extracted from the raw data with the software MassyTools. Common featuresshared by the glycan compositions were combined in 78 derived traits, includingthe number of antennae of complex-type glycans and levels of fucosylation,bisection, galactosylation, and sialylation. Associations of plasma N-glycomeswith age, sex, CD, UC and IBD-related parameters such as disease location,surgery and medication, level of C-reactive protein, and sedimentation ratewere tested by linear and logistic regression.

方法：

我們採用連鎖特異唾液酸衍生技術，對2635例炎症性腸病患者和996例對照者的的總血漿N-糖蛋白進行了質譜分析。血漿標本來自義大利的2家醫院（檢測組，1989例IBD患者和570例對照者）和1個美國的醫療中心（驗證組，646例IBD患者和426例對照者）。63種糖型符合我們的相對定量標準，並使用MassyTools軟體將其從原始數據中提取出來。聚糖複合物的共同特徵在78種衍生特徵中組合，包括複合型聚糖的觸角數目以及岩藻糖基化、對切、半乳糖基化和唾液酸化的水平。通過線性和邏輯回歸方法測試血漿N-糖蛋白與年齡、性別、CD、UC及IBD相關參數（例如病灶位置，手術和藥物，C-反應蛋白水平和沉降速率）之間的關係。

RESULTS:

Plasma samplesfrom patients with IBD had a higher abundance of large-size glycans comparedwith controls, a decreased relative abundance of hybrid and high-mannosestructures, lower fucosylation, lower galactosylation, and higher sialylation(alpha2,3- and alpha2,6-linked). We could discriminate plasma from patientswith CD from that of patients with UC based on higher bisection, lowergalactosylation and higher sialylation (alpha2,3-linked). Glycosylationpatterns associated with disease location and progression, the need for a morepotent medication, and surgery. These results were replicated in a largeindependent cohort.

結果：

來自IBD患者的血漿標本與對照組相比具有更多的大聚糖、雜合體和高甘露糖結構的相對丰度降低、岩藻糖基化較低、半乳糖基化較低以及較高的唾液酸化（alpha2,3- 和alpha2,6-鏈接）。We could discriminate plasma from patients with CD from that ofpatients with UC based on higher bisection, lower galactosylation and highersialylation (alpha2,3-linked). 基於更高的對切，更低的半乳糖基化和更高的唾液酸化（alpha 2,3-連接），我們可以區分CD患者和UC患者的血漿。 Glycosylation patterns associatedwith disease location and progression, the need for a more potent medication,and surgery. These results were replicated in a large independent cohort. 糖基化模式與病灶位置和疾病進展、更有效藥物的需求和手術相關。這些結果被複制到一個大型的獨立隊列中。

CONCLUSIONS:

We performedhigh-throughput analysis to compare total plasma N-glycomes of individuals withvs. without IBD and to identify patterns associated with disease features andthe need for treatment. These profiles might be used in diagnosis and forpredicting patients" response to treatment.

結論：

我們進行了高通量分析來比較IBD患者和未患IBD者的總血漿N-糖蛋白，並確定與疾病特徵和治療需求相關的模式。這些資料可被用於診斷和預測患者對治療的反應。

KEYWORDS:

MALDI-TOF-MS;acute phase proteins; immunoglobulins; molecular marker

關鍵詞：

MALDI-TOF-MS;急性期蛋白質;免疫球蛋白; 分子標記