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.

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