Costa, DanielBonet, NúriaSolé, AmandaGonzález de Aledo-Castillo, José ManuelSabidó Aguadé, Eduard, 1981-Casals López, FerranRovira, CarlotaNadal, AlfonsMarin, Jose LuisCobo, TeresaCastelo Valdueza, Robert2020-11-062020-11-062021Costa D, Bonet N, Solé A, González de Aledo-Castillo JM, Sabidó E, Casals F, Rovira C, Nadal A, Marin JL, Cobo T, Castelo R. Genome-wide postnatal changes in immunity following fetal inflammatory response. FEBS J. 2021 Apr;288(7):2311-31. DOI: 10.1111/febs.155781742-464Xhttp://hdl.handle.net/10230/45666The 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).application/pdfeng© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/febs.15578Fetal inflammatory responsePostnatal immunityPreterm birthProteomicsTranscriptomicsinfo:eu-repo/semantics/openAccess