Related Experiment Video
Updated: Jan 3, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Copper and selenium status as biomarkers of neonatal infections
Julian Hackler1, Monika Wisniewska1, Lennart Greifenstein-Wiehe1
1Institute for Experimental Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Insights
Early-onset sepsis (EOS) diagnosis in newborns can be improved by measuring the ceruloplasmin (CP) to selenoprotein P (SELENOP) ratio. This novel biomarker shows promise for identifying EOS in severely ill infants.
Area of Science:
- Biochemistry and Clinical Diagnostics
- Neonatal Medicine
- Trace Element Metabolism
Background:
- Neonatal infections, particularly early-onset sepsis (EOS), are a significant cause of neonatal mortality.
- Diagnosing EOS is challenging due to variable clinical presentations in newborns.
- Alterations in selenium (Se) and copper (Cu) status, and their associated proteins, may serve as diagnostic indicators for EOS.
Purpose of the Study:
- To investigate the potential of selenium (Se) and copper (Cu) status, and their related biomarkers selenoprotein P (SELENOP) and ceruloplasmin (CP), as informative markers for early-onset sepsis (EOS).
- To develop and validate a novel human CP-specific immunoassay (ELISA) for analyzing small sample volumes.
- To evaluate the diagnostic value of individual biomarkers and their ratios for EOS detection.
Main Methods:
- Development and validation of a novel human CP-specific non-competitive immunoassay (ELISA) for small sample volumes.
- Analysis of a case-control study involving 19 control newborns and 18 suspected EOS cases.
- Measurement of Se, Cu, SELENOP, CP, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations, along with Cu/Se and CP/SELENOP ratios.
- Correlation and receiver operating characteristic (ROC) curve analyses were performed to assess biomarker utility.
Main Results:
- The novel CP-ELISA demonstrated a wide working range and required minimal sample volume (2 μL).
- Plasma CP concentrations positively correlated with Cu levels (Pearson r = 0.8355, p < 0.0001).
- Three infected neonates showed significantly elevated Cu/Se and CP/SELENOP ratios (3.8- to 6.9-fold higher than controls).
- The CP/SELENOP ratio correlated positively with the acute-phase protein CRP (Spearman ϱ = 0.571, p = 0.013), indicating potential as an infection marker.
Conclusions:
- A robust, scalable, and sample-efficient CP sandwich ELISA was established for research purposes.
- The ratio of circulating ceruloplasmin (CP) to selenoprotein P (SELENOP) shows promise as a novel composite biomarker for detecting early-onset sepsis (EOS), particularly in severely ill infants.
- Combined Se and Cu status biomarkers did not significantly improve early EOS identification compared to individual markers or ratios.
Abstract:
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.
