Zhang Fan, Zhang Qian-Wen, Wang Na-Na, Liu Qian, Shen Jie, Hou Miao, Sun Ling, Lyu Hai-Tao, Yan Wen-Hua, Huang Jie
Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2022 Apr 15;24(4):392-398. doi: 10.7499/j.issn.1008-8830.2110110.
To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.
In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.
A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.
The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.
研究川崎病（KD）急性期患儿血清外泌体的生物学过程及功能，为KD的早期诊断提供新的生物标志物。
本前瞻性研究纳入2019年6月至2020年8月在苏州大学附属儿童医院接受治疗的13例KD患儿作为KD组，同期因细菌感染住院的13例患儿作为对照组。入院次日清晨采集全血，离心获得血清样本，通过超速离心提取外泌体。采用无标记定量蛋白质组学分析血清外泌体，筛选差异表达蛋白（DEPs）进行功能富集分析。绘制蛋白质-蛋白质相互作用（PPI）网络，并通过靶向蛋白质组学验证独特蛋白。
两组共筛选出131个DEPs，其中两组均检测到27种蛋白。KD组有48个独特的DEPs，其中23个上调，25个下调，这些蛋白作用于“补体和凝血级联反应”及“MAPK信号通路”。靶向蛋白质组学验证显示，KD组中FGG、SERPING1、C1R、C1QA、IGHG4和C1QC蛋白可定量。对照组共有29种蛋白仅表达，其中12个上调，17个下调。基于靶向蛋白质组学有4种蛋白可定量，即VWF、ECM1、F13A1和TTR。为每组绘制PPI网络。在KD组中，FGG和C1QC与其他蛋白有密切相互作用，而在对照组中，VWF与其他蛋白有密切相互作用。
KD急性期患儿血清外泌体FGG和C1QC有望成为KD早期诊断的生物标志物。对于不明原因发热的患儿，检测FGG、C1QC和VWF可能有助于病因筛查。
