Copper and selenium status as biomarkers of neonatal infections
Copper and selenium status as biomarkers of neonatal infections
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DOI：
10.1016/j.jtemb.2019.126437
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发表时间：
2020-03-01
影响因子：
3.5
通讯作者：
Schomburg, Lutz
中科院分区：
文献类型：
--
作者：
Hackler, Julian;Wisniewska, Monika;Schomburg, Lutz
新生儿感染是新生儿死亡的一个主要危险因素。一个可靠的诊断早发性脓毒症（EOS）是阻碍了可变的临床表现的儿童。我们假设，硒或铜状态的变化，或生物标志物硒蛋白P（SELENOP）或铜蓝蛋白（CP）单独或组合可能是有用的EOS.We产生了一种新的人类CP特异性非竞争性免疫测定（ELISA）适合分析小样本量和验证的方法与商业CP源。使用这种新的CP检测，我们分析了EOS的病例对照研究（n = 19例对照新生儿，n = 18例疑似病例）。通过相关性分析评估Se、Cu、SELENP、CP、白细胞介素-6（IL-6）和C反应蛋白（CRP）的浓度沿着Cu/Se和CP/SELENP比值，作为EOS的生物标志物。新的CP-ELISA显示了较宽的工作范围（0.10-6.78 mg CP/L）和较低的样品要求（2 μ L血清、EDTA-、肝素-或柠檬酸-血浆）。在所有样本组中，血浆CP与Cu浓度呈正相关（Pearson r = 0.8355，p< 0.0001）。三个感染的新生儿显示出特别高的Cu/Se和CP/SELENP比率，即，3.8-比对照组高6.9倍。Cu/Se和CP/SELENOP-CRP比值与早期感染标志物IL-6的相关性较差，但与急性时相蛋白CRP的相关性较强且呈正相关（Cu/Se-CRP：斯皮尔曼（sic）=0.583，p = 0.011; CP/SELENOP-CRP：（sic）= 0.571，p = 0.013）。ROC曲线分析表明，硒和铜状态的生物标志物的组合并不能提高EOS的早期识别显着。这项研究建立了一个强大的，高度精确的，部分验证和可扩展的新的CP夹心ELISA适用于基础和临床研究，需要微量的样品。循环CP/SELENOP的比值构成了一种有前途的新的复合生物标志物，用于检测EOS，至少在一部分严重疾病儿童中是如此。
Neonatal infections are a major risk factor for neonatal mortality. A reliable diagnosis of early-onset sepsis (EOS) is hampered by the variable clinical presentations of the children. We hypothesized that changes in the Se or Cu status, or the biomarkers selenoprotein P (SELENOP) or ceruloplasmin (CP) alone or in combination may be informative of EOS.We generated a new human CP-specific non-competitive immunoassay (ELISA) suitable of analysing small sample volumes and validated the method with a commercial CP source. Using this novel CP assay, we analysed a case-control study of EOS (n = 19 control newborns, n = 18 suspected cases). Concentrations of Se, Cu, SELENOP, CP, interleukin-6 (IL-6), and C-reactive protein (CRP) along with the Cu/Se and CP/SELENOP ratios were evaluated by correlation analyses as biomarkers for EOS. Diagnostic value was estimated by receiver operating characteristic (ROC) curve analyses.The new CP-ELISA displayed a wide working range (0.10-6.78 mg CP/L) and low sample requirement (2 mu L of serum, EDTA-, heparin- or citrate-plasma). Plasma CP correlated positively with Cu concentrations in the set of all samples (Pearson r = 0.8355, p< 0.0001). Three of the infected neonates displayed particularly high ratios of Cu/Se and CP/SELENOP, i.e., 3.8- to 6.9-fold higher than controls. Both the Cu/Se and the CP/SELENOP ratios correlated poorly with the early infection marker IL-6, but strongly and positively with the acute-phase protein CRP (Cu/Se-CRP: Spearman (sic) =0.583, p = 0.011; CP/SELENOP-CRP:(sic) = 0.571, p = 0.013). The ROC curve analyses indicate that a combination of biomarkers for the Se and Cu status do not improve the early identification of EOS considerably.This study established a robust, highly precise, partly validated and scalable novel CP sandwich ELISA suitable for basic and clinical research, requiring minute amounts of sample. The ratio of circulating CP/SELENOP constitutes a promising new composite biomarker for detection of EOS, at least in a subset of severely diseased children.