铜和硒状态是新生儿感染的生物标志物。,Journal of Trace Elements in Medicine and Biology

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铜和硒状态是新生儿感染的生物标志物。
Journal of Trace Elements in Medicine and Biology ( IF 3.6 ) Pub Date : 2019-11-15 , DOI: 10.1016/j.jtemb.2019.126437
Julian Hackler ₁ , Monika Wisniewska ₁ , Lennart Greifenstein-Wiehe ₁ , Waldemar B Minich ₁ , Malte Cremer ₂ , Christoph Bührer ₂ , Lutz Schomburg ₁

Affiliation

新生儿感染是新生儿死亡的主要危险因素。儿童可变的临床表现妨碍了早发性败血症（EOS）的可靠诊断。我们假设硒或铜状态的改变或单独或组合使用的生物标志物硒蛋白P（SELENOP）或铜蓝蛋白（CP）可能对EOS有用。我们生成了一种适用于分析少量样品的新型人类CP特异性非竞争性免疫测定（ELISA），并使用商业CP来源验证了该方法。使用这种新颖的CP分析，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）。通过相关分析评估E，E，S，Cu，SELENOP，CP，白介素6（IL-6）和C反应蛋白（CRP）的浓度以及Cu / Se和CP / SELENOP的比例。通过接收器工作特性（ROC）曲线分析来估计诊断值。新的CP-ELISA显示了较宽的工作范围（0.10-6.78 mg CP / L）和较低的样品需求量（2μL血清，EDTA，肝素或柠檬酸盐血浆）。血浆CP与所有样品中的铜浓度呈正相关（Pearson r = 0.8355，p <0.0001）。其中三个被感染的新生儿表现出特别高的Cu / Se和CP / SELENOP比例，即比对照组高3.8至6.9倍。Cu / Se和CP / SELENOP比率与早期感染标志物IL-6的相关性较弱，但与急性期蛋白CRP的相关性强且呈正相关（Cu / Se-CRP：Spearman ϱ = 0.583，p = 0.011; CP / SELENOP-CRP：ϱ = 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不能显着改善EOS的早期识别。这项研究建立了一种健壮，高度精确，经过部分验证和可扩展的新型CP夹心ELISA，适用于基础和临床研究，需要少量样品。循环CP / SELENOP的比率构成了一种有希望的新的复合生物标记物，至少在一部分重症儿童中可用于检测EOS。

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Copper and selenium status as biomarkers of neonatal infections.

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 μL 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 ϱ = 0.583, p = 0.011; CP/SELENOP-CRP: ϱ = 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.

更新日期：2019-11-18

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