Copper and selenium status as biomarkers of neonatal infections

Julian Hackler; Monika Wisniewska; Lennart Greifenstein-Wiehe; Waldemar B Minich; Malte Cremer; Christoph Bührer; Lutz Schomburg

doi:10.1016/j.jtemb.2019.126437

Copper and selenium status as biomarkers of neonatal infections

J Trace Elem Med Biol. 2020 Mar:58:126437. doi: 10.1016/j.jtemb.2019.126437. Epub 2019 Nov 15.

Authors

Julian Hackler¹, Monika Wisniewska¹, Lennart Greifenstein-Wiehe¹, Waldemar B Minich¹, Malte Cremer², Christoph Bührer², Lutz Schomburg³

Affiliations

¹ Institute for Experimental Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
² Department of Neonatology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
³ Institute for Experimental Endocrinology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address: lutz.schomburg@charite.de.

PMID: 31778962
DOI: 10.1016/j.jtemb.2019.126437

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.

Keywords: Ceruloplasmin; Composite biomarker; Early onset infection; Point-of-care test; Selenoprotein P; Trace element.

MeSH terms

Biomarkers / blood
C-Reactive Protein / metabolism
Case-Control Studies
Ceruloplasmin / metabolism
Copper / blood*
Enzyme-Linked Immunosorbent Assay
Humans
Infant, Newborn
Infant, Newborn, Diseases / blood*
Infections / blood*
Interleukin-6 / blood
Selenium / blood*
Selenoprotein P / blood
Trace Elements / blood

Substances

Biomarkers
Interleukin-6
Selenoprotein P
Trace Elements
Copper
C-Reactive Protein
Ceruloplasmin
Selenium