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免疫球蛋白是参与肝硬化患者血清总 N-糖组修饰的主要糖蛋白。

Immunoglobulins are the major glycoproteins involved in the modifications of total serum N-glycome in cirrhotic patients.

机构信息

Laboratoire de Biochimie et de Biologie Moléculaire, UAM de glycopathologies, Centre de Biologie et Pathologies, CHRU Lille, Bld du Professeur Jules Leclercq, Lille, France.

出版信息

Proteomics Clin Appl. 2010 Apr;4(4):379-93. doi: 10.1002/prca.200900133. Epub 2010 Feb 3.

Abstract

PURPOSE

N-glycosylation modifications in human serum glycoproteins have been described in hepatic cirrhosis. To identify the glycoproteins carrying these modifications and to determine their influences in the modification of the total serum N-glycome (TSNG) in cirrhotic patients, we have performed the glycosylation analysis of immunoglobulins, transferrin, 1 antitrypsin and haptoglobin of patients who have developed cirrhosis.

EXPERIMENTAL DESIGN

The glycosylation analysis of immunoglobulins G, transferrin, 1 antitrypsin and haptoglobin of 14 patients who have developed cirrhosis and 11 healthy controls was performed using strategies based on MS, 2-DE and affinity chromatography.

RESULTS

We demonstrated that the N-glycosylation of both hepatic and plasma cell secreted glycoproteins is modified, and that the major modifications of TSNG are carried by immunoglobulins A and G.

CONCLUSIONS AND CLINICAL RELEVANCE

The search for glycomic biomarkers used as an alternative to liver biopsy for the assessment of fibrosis in chronic liver disease is extremely important. Variations in the glycosylation of immunoglobulins are responsible for the main modifications affecting the TSNG and effector properties of the Fc of these molecules, and certainly contribute to the pathophysiology of fibrosis.

摘要

目的

已在肝硬化患者的血清糖蛋白中描述了 N-糖基化修饰。为了鉴定携带这些修饰的糖蛋白,并确定它们在肝硬化患者总血清 N-糖组(TSNG)修饰中的影响,我们对已发生肝硬化的患者的免疫球蛋白、转铁蛋白、1 抗胰蛋白酶和触珠蛋白进行了糖基化分析。

实验设计

我们使用基于 MS、2-DE 和亲和层析的策略,对 14 名已发生肝硬化的患者和 11 名健康对照者的免疫球蛋白 G、转铁蛋白、1 抗胰蛋白酶和触珠蛋白进行了糖基化分析。

结果

我们证明了肝和浆细胞分泌的糖蛋白的 N-糖基化均发生了修饰,并且 TSNG 的主要修饰由免疫球蛋白 A 和 G 携带。

结论和临床相关性

寻找糖组生物标志物作为肝活检的替代方法,用于评估慢性肝病中的纤维化,这一点极其重要。免疫球蛋白糖基化的变化导致了影响 TSNG 的主要修饰以及这些分子的 Fc 的效应特性,并且肯定有助于纤维化的病理生理学。

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