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川崎病患者静脉注射免疫球蛋白治疗后血清外泌体的差异蛋白质分析

Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease.

作者信息

Zhang Li, Song Qi-Fang, Jin Jing-Jie, Huang Ping, Wang Zhou-Ping, Xie Xiao-Fei, Gu Xiao-Qiong, Gao Xue-Juan, Jia Hong-Ling

机构信息

1Guangzhou Women and Children's Medical Center,Guangzhou 510120,Guangdong,China.

2Department of Bioengineering,Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering,Jinan University,Guangzhou 510632,Guangdong,China.

出版信息

Cardiol Young. 2017 Nov;27(9):1786-1796. doi: 10.1017/S1047951117001433. Epub 2017 Aug 14.

Abstract

BACKGROUND

Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin.

METHODS

Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy.

RESULTS

Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function.

CONCLUSIONS

Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.

摘要

背景

川崎病以伴有急性发热的系统性血管炎为特征,通常采用静脉注射免疫球蛋白进行治疗以避免冠状动脉病变形成;然而,静脉注射免疫球蛋白治疗的机制尚不清楚。因此,我们旨在分析静脉注射免疫球蛋白前后血清外泌体蛋白质的整体表达谱。

方法

采用二维电泳结合质谱分析来鉴定川崎病患者静脉注射免疫球蛋白治疗前后血清外泌体中差异表达的蛋白质组。

结果

我们的分析显示,与对照组相比,川崎病组有69个差异蛋白点变化大于1.5倍,静脉注射免疫球蛋白治疗后的患者有59个差异蛋白点。基因本体分析显示,静脉注射免疫球蛋白后急性期反应消失,补体系统和先天免疫反应功能增强,出现了皮质类固醇的抗菌体液反应途径和心脏保护作用。此外,我们发现补体C3和载脂蛋白A-IV水平在静脉注射免疫球蛋白治疗前升高,治疗后降低,胰岛素样生长因子结合蛋白复合物酸性不稳定亚基在静脉注射免疫球蛋白治疗前后表现出相反的变化。这些观察结果可能是静脉注射免疫球蛋白功能的潜在指标。

结论

我们的结果显示了川崎病患者静脉注射免疫球蛋白治疗前后血清外泌体的差异蛋白质组学特征,如补体C3、载脂蛋白A-IV和胰岛素样生长因子结合蛋白复合物酸性不稳定亚基。这些结果可能有助于识别监测川崎病患者静脉注射免疫球蛋白治疗的标志物。

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