Zhang Li, Jia Hong-Ling, Huang Wei-Min, Liu Chao-Wu, Hua Liang, Liu Te-Chang, Mao Li-Jia, Xu Yu-Fen, Li Wei, Xia Shu-Liang, Gan Ying-Yan, Deng Li, Zhang Gong
Guangzhou Women and Children's Medical Center, Guangzhou 510120, Guangdong, China.
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
Biochem Biophys Res Commun. 2014 Apr 25;447(1):19-25. doi: 10.1016/j.bbrc.2014.03.108. Epub 2014 Mar 29.
Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. The causal pathogen is unknown, therefore specific diagnostic biomarkers and therapy are unavailable. High-dose intravenous immunoglobulin (IVIG) is considered as the most effective therapy to reduce the prevalence of coronary artery lesion (CAL) in KD; however, it has side effects. This study aimed to (1) determine whether IVIG therapy is effective at the molecular level; (2) provide the first serum proteomic profile of KD under IVIG therapy; and (3) screen for monitoring biomarker candidates. We extracted serum proteins from samples of healthy individuals and from KD patients before and after IVIG therapy, and employed two-dimensional electrophoresis and MALDI-TOF/TOF mass spectrometry to identify differentially expressed proteins. The identifications were validated by Western blotting. We identified 29 differentially expressed proteins in KD patients and found that IVIG therapy restored most of these proteins to near-normal levels. Tracing the protein levels of single patients before and after IVIG therapy showed that the proteins, especially Transthyretin (TTR), are potential markers for therapeutic monitoring. Functional analyses of these proteins by PANTHER and String suggested that the key influence of KD lay in the immune system, which was targeted by IVIG.
川崎病（KD）是一种主要影响5岁以下儿童的全身性血管炎。其致病病原体尚不清楚，因此缺乏特异性诊断生物标志物和治疗方法。大剂量静脉注射免疫球蛋白（IVIG）被认为是降低KD患者冠状动脉病变（CAL）发生率最有效的治疗方法；然而，它有副作用。本研究旨在：（1）确定IVIG治疗在分子水平上是否有效；（2）提供IVIG治疗下KD患者的首个血清蛋白质组图谱；（3）筛选监测生物标志物候选物。我们从健康个体以及IVIG治疗前后的KD患者样本中提取血清蛋白，并采用二维电泳和基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF）来鉴定差异表达蛋白。通过蛋白质印迹法对鉴定结果进行验证。我们在KD患者中鉴定出29种差异表达蛋白，并发现IVIG治疗使这些蛋白中的大多数恢复到接近正常水平。追踪单个患者IVIG治疗前后的蛋白水平表明，这些蛋白，尤其是转甲状腺素蛋白（TTR），是治疗监测的潜在标志物。通过PANTHER和String对这些蛋白进行功能分析表明，KD的关键影响在于免疫系统，而IVIG正是作用于该系统。
