Early detection of neonatal group B streptococcus sepsis and the possible diagnostic utility of IL-6, IL-8, and CD11b in a human umbilical cord blood in vitro model
Authors Nakstad B, Sonerud T, Solevag AL
Received 10 February 2016
Accepted for publication 8 April 2016
Published 8 July 2016 Volume 2016:9 Pages 171—179
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Suresh Antony
Britt Nakstad,1,2 Tonje Sonerud,1,3 Anne Lee Solevåg1
1Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, 2Institute of Clinical Medicine, University of Oslo, Lørenskog, 3Section of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, Lørenskog, Norway
Background: Group B streptococcus (GBS) infection remains a major cause of neonatal morbidity and mortality, and GBS III is the predominant strain in early-onset GBS neonatal sepsis. To avoid both over- and undertreatment of infants with nonspecific signs of infection, early diagnostic tools are warranted. The aim of this study was to identify biomarkers with high sensitivity and specificity in an early stage of GBS infection. A secondary aim was to assess the utility of a human umbilical cord blood (HUCB) model system of early-onset neonatal sepsis.
Methods: Umbilical cord blood samples from 20 healthy term pregnancies were stimulated for 2 hours with a GBS III isolate from a patient and a commercially available GBS Ia strain. Nonstimulated samples served as controls. Leukocyte surface markers (CD11b, CD64, toll-like receptor [TLR] 2, TLR4, and TLR6) were analyzed by flow cytometry and soluble biomarkers by enzyme-linked immunosorbent assay (interleukin [IL]-6 and -8; interferon-γ-inducing protein [IP]-10; and S100b). The area under the receiver operating characteristic curve (AUC) was calculated for the markers.
Results: GBS III gave the highest responses and AUC values for all biomarkers. Only IL-6 and IL-8 displayed an AUC approaching 0.8 for both GBS serotypes (P<0.001). IL-8 >5,292 pg/mL had both a sensitivity and a specificity of 1.00. IL-6 >197 pg/mL had both a sensitivity and a specificity of 0.95 for GBS III stimulation. CD11b on granulocytes and monocytes was the leukocyte surface marker with the highest AUC values for both GBS serotypes.
Conclusion: In agreement with previous studies, IL-6, IL-8, and potentially CD11b could be useful in diagnosing neonatal GBS infection in an early stage. Our HUCB early-onset neonatal sepsis model may be useful for evaluating biomarkers of neonatal sepsis. The HUCB of neonates with risk factors for sepsis might even be used for diagnostic purposes, but requires further study.
Keywords: TLR4, TLR6, CD64, GBS serotypes, flow cytometry
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