Markers of NETosis Do Not Predict Neonatal Early Onset Sepsis: A Pilot Study

Stiel, Carolin; Ebenebe, Chinedu Ulrich; Trochimiuk, Magdalena; Raluy, Laia Pagarols; Vincent, Deirdre; Singer, Dominique; Reinshagen, Konrad; Boettcher, Michael

doi:10.3389/fped.2019.00555

Cited by 7 publications

(7 citation statements)

References 25 publications

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“…Therefore, our findings indicate that neonates may have a lower capacity to fight these bacteria. In contrast, Stiel et al [ 39 ] reported that NET markers (e.g., NE, MPO, and cell-free DNA) in umbilical cord blood do not appear to be a predictor of the onset of neonatal sepsis within 72 h postpartum. This is in contrast with newer experimental data from Colón et al, which showed that infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than adult mice [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

et al. 2022

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The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23–36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.

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Section: Discussionmentioning

confidence: 99%

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

et al. 2022

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“…These findings must be interpreted with caution, because of the low sample size included in the study. In a previous study, NET markers in umbilical cord blood drawn immediately after birth were unable to predict future EONS in neonates [ 17 ]. The main reason may be that prenatal NET formation is limited by the neonatal NET inhibitory factor (nNIF), which can be found in cord blood samples of neonates [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…All data were analyzed using SPSS Statistics 26 (IBM, Armonk, NY, USA) and GraphPad Prism 9 (GraphPad, San Diego, CA, USA). As this was a pilot study, power estimation was deduced from previous trials regarding sepsis in neonates [ 17 ]. Differences between groups were calculated using Mann–Whitney tests.…”

Section: Methodsmentioning

confidence: 99%

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

Lenz

Maiberger²,

Armbrust

et al. 2022

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Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. Methods: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). Results: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.

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“…In 2020, Stiel et al collected statistics of complete blood count, C-reactive protein (CRP), IL-6, levels of cell-free DNA (cfDNA), neutrophil elastase (NE) and myeloperoxidase (MPO) in umbilical cord blood to try to predict the early-onset sepsis. Unfortunately, the markers of NETosis they testified could not predict the happening of sepsis (149).…”

Section: Clinical Research Statusmentioning

confidence: 99%

The “Self-Sacrifice” of ImmuneCells in Sepsis

et al. 2022

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Sepsis is a life-threatening organ dysfunction caused by the host’s malfunctioning response to infection. Due to its high mortality rate and medical cost, sepsis remains one of the world’s most intractable diseases. In the early stage of sepsis, the over-activated immune system and a cascade of inflammation are usually accompanied by immunosuppression. The core pathogenesis of sepsis is the maladjustment of the host’s innate and adaptive immune response. Many immune cells are involved in this process, including neutrophils, mononuclear/macrophages and lymphocytes. The immune cells recognize pathogens, devour pathogens and release cytokines to recruit or activate other cells in direct or indirect manner. Pyroptosis, immune cell-extracellular traps formation and autophagy are several novel forms of cell death that are different from apoptosis, which play essential roles in the progress of sepsis. Immune cells can initiate “self-sacrifice” through the above three forms of cell death to protect or kill pathogens. However, the exact roles and mechanisms of the self-sacrifice in the immune cells in sepsis are not fully elucidated. This paper mainly analyzes the self-sacrifice of several representative immune cells in the forms of pyroptosis, immune cell-extracellular traps formation and autophagy to reveal the specific roles they play in the occurrence and progression of sepsis, also to provide inspiration and references for further investigation of the roles and mechanisms of self-sacrifice of immune cells in the sepsis in the future, meanwhile, through this work, we hope to bring inspiration to clinical work.

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Markers of NETosis Do Not Predict Neonatal Early Onset Sepsis: A Pilot Study

Cited by 7 publications

References 25 publications

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

The “Self-Sacrifice” of ImmuneCells in Sepsis

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