Li Jieqiong, Sun Lin, Xu Fang, Qi Hui, Shen Chen, Jiao Weiwei, Xiao Jing, Li Qinjing, Xu Baoping, Shen Adong
MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics (Capital Medical University), National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University Beijing, China.
Front Microbiol. 2016 Dec 15;7:1961. doi: 10.3389/fmicb.2016.01961. eCollection 2016.
Although (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.
虽然支原体肺炎（MP）是儿童社区获得性肺炎（CAP）的常见病因，但目前使用的诊断方法并不理想。蛋白质组学越来越多地用于研究传染病的生物标志物。采用无标记定量蛋白质组学和液相色谱-质谱/质谱联用技术分析MP肺炎（MPP）患儿、传染病对照组（IDC）和健康对照组（HC）血浆中蛋白质表达的倍数变化。通过酶联免疫吸附测定（ELISA）进一步验证可区分MPP与HC和IDC的选定蛋白质。经过多变量分析，确定了27种潜在的血浆生物标志物在儿童MPP、HC和IDC组中表达存在差异。在这些蛋白质中，选择了丝氨酸蛋白酶抑制剂A3（SERPINA3）、载脂蛋白C1（APOC1）、膜联蛋白A6（ANXA6）、驱动蛋白家族成员1（KNTC1）和细胞凋亡相关富含半胱氨酸的蛋白（CFLAR）进行ELISA验证。SERPINA3、APOC1和CFLAR水平在三组之间存在显著差异，且比值与蛋白质组学结果趋势一致。MPP患者与HC的比较显示，APOC1的曲线下面积（AUC）最大，为0.853，敏感性为77.6%，特异性为81.1%。当比较MPP与IDC患者的APOC1水平时，其AUC也相对较高，为0.882，敏感性为77.6%，特异性为85.3%。APOC1是儿童MPP快速无创诊断的潜在生物标志物。本研究结果可能为儿童MPP的发病机制和生物标志物选择提供新的见解。
