Identification of Diagnostic Biomarkers for Infection in Premature Neonates
Identification of Diagnostic Biomarkers for Infection in Premature Neonates
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DOI：
10.1074/mcp.m800175-mcp200
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发表时间：
2008-10-01
影响因子：
7
通讯作者：
Edgar, J. David M.
中科院分区：
文献类型：
--
作者：
Kingsmore, Stephen F.;Kennedy, Neil;Edgar, J. David M.
感染是全世界新生儿发病和死亡的主要原因。由于生理不成熟、合并症和外部医疗干预，早产儿特别容易受到感染。此外，早产儿进展为败血症或严重败血症、不良后果和抗菌药物毒性的风险较高。目前，初步诊断是基于临床怀疑并伴有非特异性临床症状，并在开始经验性治疗几天后根据微生物培养阳性结果得到确认。迫切需要快速、客观的体外测试来诊断临床不稳定的新生儿的感染。我们使用微阵列上的多重免疫测定来识别临床感染和未感染新生儿中差异表达的血清蛋白。免疫分析阵列可有效测量新生儿小体积血清中的 100 多种细胞因子。我们的分析显示，受感染新生儿的八种血清蛋白水平发生显着变化，这些变化与炎症、凝血和纤维蛋白溶解有关。具体而言，观察到P-和E-选择素、白细胞介素2可溶性受体α、白细胞介素18、中性粒细胞弹性蛋白酶、尿激酶纤溶酶原激活剂及其同源受体以及C反应蛋白的水平显着升高。基于血清分析物组合的多变量分类器比单一分析物表现出更好的诊断特异性和敏感性。血清细胞因子的多重免疫测定可能具有临床实用性，可作为临床失代偿新生儿感染的快速诊断和病原体鉴别的辅助手段。分子与细胞蛋白质组学 7：1863-1875，2008。
Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation. Molecular & Cellular Proteomics 7: 1863-1875, 2008.