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Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates

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European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Neonatal early-onset sepsis (EOS) is associated with high morbidity and mortality. Accurate early diagnosis is crucial for prompt treatment and a better clinical outcome. We aimed to identify new biomarkers for the diagnosis of EOS. A total of 152 neonates with a risk of EOS were divided into an EOS group and a non-EOS group according to the conventional diagnostic criteria. Blood samples were collected within 0–24, 24–48, and 48–72 h after birth. Serum levels of progranulin (PGRN), interleukin (IL)-33, IL-17a, IL-23, IL-6, tumor necrosis factors α (TNF-α), interferon γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), procalcitonin (PCT), and C-reactive protein (CRP) were determined. PGRN levels were significantly elevated in the EOS neonates compared with the levels in the non-EOS neonates (1.53 vs. 0.77 ng/ml (median), P < 0.001), with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.76 (P < 0.001). Compared with PGRN, IL-33, IL-17a, IL-23, IL-6, PCT, and CRP showed significant (AUC > 0.70) but slightly less predictive power for EOS within the same time range. Stepwise multivariate regression analysis identified PGRN, IL-33, and PCT as independent predictors of EOS. In addition, the combined measurements of PGRN, IL-33, and PCT showed significantly higher predictive power for EOS than any of the three markers alone. PGRN showed greater efficacy for predicting EOS than the traditional markers PCT and CRP as well as other potential markers tested in this study. PGRN may serve as an effective biomarker for the early diagnosis of EOS.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

EOS:

early-onset sepsis

PGRN:

progranulin

IL-33:

interleukin 33

IL-17a:

interleukin 17a

IL-23:

interleukin 23

IL-6:

interleukin 6

TNF-α:

tumor necrosis factors α

IFN-γ:

interferon γ

GM-CSF:

granulocyte-macrophage colony-stimulating factor

PCT:

procalcitonin

CRP:

C-reactive protein

AUC:

area under the curve

CI:

confidence interval

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Funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81571483 and 81971431) and Shenzhen Science and Technology Innovation Free Exploration Project (JCYJ20170817100735621).

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Authors and Affiliations

  1. Department of Neonatology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Road, Yuzhong District, Chongqing, 400014, China

    Kai-Di Yang, Yu He, Sa Xiao, Qing Ai & Jia-Lin Yu

  2. Department of Pediatrics, Shenzhen University General Hospital, Shenzhen, Guangdong, China

    Jia-Lin Yu

  3. Chongqing Key Laboratory of Pediatrics, Chongqing, China

    Kai-Di Yang, Yu He, Sa Xiao, Qing Ai & Jia-Lin Yu

  4. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China

    Kai-Di Yang, Yu He, Sa Xiao, Qing Ai & Jia-Lin Yu

  5. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China

    Kai-Di Yang, Yu He, Sa Xiao, Qing Ai & Jia-Lin Yu

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  1. Kai-Di Yang
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  2. Yu He
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Contributions

KY, YH, and JY contributed to the conception of the study. KY contributed significantly to analysis and manuscript preparation; KY performed the data analyses and wrote the manuscript; SX, QA, and JY helped perform the analysis with constructive discussions. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jia-Lin Yu.

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Ethics approval

This study was approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University (2015-115).

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The consent to participate had been obtained from all the legal guardian of the patients.

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The authors declare that they have no competing interests.

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Yang, KD., He, Y., Xiao, S. et al. Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates. Eur J Clin Microbiol Infect Dis 39, 2405–2414 (2020). https://doi.org/10.1007/s10096-020-03981-x

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  • DOI: https://doi.org/10.1007/s10096-020-03981-x

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