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Genome-wide postnatal changes in immunity following fetal inflammatory response.

Authors
  • Costa, Daniel1, 2
  • Bonet, Núria3
  • Solé, Amanda2, 4, 5
  • González de Aledo-Castillo, José Manuel6
  • Sabidó, Eduard2, 4, 5
  • Casals, Ferran3
  • Rovira, Carlota7
  • Nadal, Alfons8
  • Marin, Jose Luis9
  • Cobo, Teresa9
  • Castelo, Robert2, 10
  • 1 Department of Pediatrics, Hospital de Figueres, Spain. , (Spain)
  • 2 Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain. , (Spain)
  • 3 Genomics Core Facility, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain. , (Spain)
  • 4 Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona, Spain. , (Spain)
  • 5 Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. , (Spain)
  • 6 Inborn Errors of Metabolism Section, Laboratory of Biochemistry and Molecular Genetics, Hospital Clínic, Barcelona, Spain. , (Spain)
  • 7 Hospital Sant Joan de Déu, Barcelona, Spain. , (Spain)
  • 8 Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain. , (Spain)
  • 9 Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centre for Biomedical Research on Rare Diseases (CIBER-ER), University of Barcelona, Spain. , (Spain)
  • 10 Research Programme on Biomedical Informatics, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. , (Spain)
Type
Published Article
Journal
FEBS Journal
Publisher
Wiley (Blackwell Publishing)
Publication Date
Apr 01, 2021
Volume
288
Issue
7
Pages
2311–2331
Identifiers
DOI: 10.1111/febs.15578
PMID: 33006196
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of well-established inflammatory biomarkers in the umbilical cord and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we profiled the transcriptome and proteome of archived neonatal dried blood spot (DBS) specimens from 21 ELGANs. Comparing FIR-affected and unaffected ELGANs, we identified 782 gene and 27 protein expression changes of 50% magnitude or more, and an experiment-wide significance level below 5% false discovery rate. These expression changes confirm the robust postnatal activation of the innate immune system in FIR-affected ELGANs and reveal for the first time an impairment of their adaptive immunity. In turn, the altered pathways provide clues about the molecular mechanisms triggering ISSI after FIR, and the onset of perinatal brain injury. DATABASES: EGAS00001003635 (EGA); PXD011626 (PRIDE). © 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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