Copper and selenium status as biomarkers of neonatal infections |
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| Affiliation: | 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;1. Charité – Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany;2. Charité – Universitätsmedizin Berlin, Notfallmedizin/Rettungsstellen und Chest Pain Units, Berlin, Germany;3. Department of Intensive Care Medicine, RWTH Aachen University, Aachen, Germany;1. Department of Psychiatry, Hospital Universitario de Getafe, Carretera de Toledo km.12.5 28905, Getafe, Madrid, Spain;2. Department of Laboratory Medicine, IML, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;3. Department of Neurology, Hospital de la Zarzuela, Calle de Pléyades 25, 28023, Madrid, Spain;4. Department of Epidemiology, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;5. Department of Public Health, University Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, 28223 Pozuelo de Alarcón, Madrid, Spain;6. Department of Internal Medicine, Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;7. Department of Pediatrics, Department of Public Health, Gynecology and Pediatrics, Faculty of Medicine, Universidad Complutense de Madrid, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;1. Faculty of Medicine, Sofia University “St. Kliment Ohridski”, 1 Kozjak Street, 1407, Sofia, Bulgaria;2. Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1 James Bourchier Blvd., 1164, Sofia, Bulgaria;3. Institute of Experimental Morphology, Pathology and Anthropology with Museum – BAS, Acad. Georgi Bonchev Str., bl. 25, 1113, Sofia, Bulgaria;4. Chemistry Department, R&D, BIOVET JSC, 39 Peter Rakov Str., 4550, Peshtera, Bulgaria;1. Department of Pediatric Gastroenterology, Hepatology and Nutrition, İnönü University, Faculty of Medicine, Malatya,Turkey;2. Department of Pediatric Neurology, İnönü University, Faculty of Medicine, Malatya,Turkey;3. Department of Medicinal Biochemistry, İnönü University, Faculty of Medicine, Malatya, Turkey;1. Discipline of Pediatric Nutrition, Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil;2. Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil;1. Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 11, 1113 Sofia, Bulgaria;2. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria;3. National and Kapodistrian University of Athens, Department of Chemistry, Laboratory of Environmental Chemistry, Panepistimiopolis, 15784 Athens, Greece |
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| 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. |
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| Keywords: | Ceruloplasmin Selenoprotein P Early onset infection Point-of-care test Trace element Composite biomarker |
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