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

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

DOI:
10.1017/s1047951117001433
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发表时间:
2017-08
影响因子:
1
通讯作者:
Jia Hong-Ling
Jia Hong-Ling
中科院分区:
医学4区
文献类型:
--
作者:
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

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摘要背景川崎病以全身性血管炎伴急性发热为特征,常规静脉注射免疫球蛋白以避免冠状动脉病变的形成;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的总体表达谱。方法采用双向电泳结合质谱分析技术,对川崎患者静脉注射丙种球蛋白治疗前后血清exosomes蛋白质组差异进行鉴定。结果与对照组相比,川崎病组有69个差异蛋白质点的变化大于1.5倍,静脉注射免疫球蛋白治疗组有59个差异蛋白质点。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,补体系统和天然免疫功能增强,皮质类固醇的抗菌体液反应途径和心脏保护作用出现。此外,我们发现,补体C3和载脂蛋白A-IV水平增加之前和静脉注射免疫球蛋白治疗后下降,胰岛素样生长因子结合蛋白复合物酸不稳定亚基显示反向改变之前和之后静脉注射免疫球蛋白治疗。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。结论川崎患者静脉注射丙种球蛋白治疗前后血清外泌体蛋白质组学差异,包括补体C3、载脂蛋白A-IV、胰岛素样生长因子结合蛋白复合物酸不稳定亚基。这些结果可能是有用的识别标记物监测静脉免疫球蛋白治疗川崎患者。
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.
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DOI: --
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