Histological chorioamnionitis shapes the neonatal transcriptomic immune response.
Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis.



To define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis.



Prospective, observational study.



Uninfected preterm neonates retrospectively categorized based on placental pathology with no HCA exposure (n=18) or HCA exposure (n=15).



We measured the transcriptomic and inflammatory mediator response in prospectively collected whole blood.



We found 488 significant (p<0.001), differentially expressed genes in whole blood samples among uninfected neonates with HCA exposure that collectively represented activated innate and adaptive immune cellular pathways and revealed a potential regulatory role for the pleotropic microRNA molecule miR-155. Differentially secreted plasma cytokines in patients with HCA exposure compared to patients without HCA included MCP-1, MPO, and MMP-9 (p<0.05).



Exposure to HCA distinctively activates the neonatal immune system in utero with potentially long-term health consequences.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
Jörn-Hendrik
JH
Weitkamp
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States; Ayers Children's Medical Center, Jackson-Madison County General Hospital, Jackson, TN, United States.
Scott O
SO
Guthrie
Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Hector R
HR
Wong
Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States.
Lyle L
LL
Moldawer
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, United States.
Henry V
HV
Baker
Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, United States; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States. Electronic address: james.wynn@peds.ufl.edu.
James L
JL
Wynn
D056704:Adaptive Immunity; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D002821:Chorioamnionitis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D059467:Transcriptome
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Histologic chorioamnionitis; Neonate; Premature; Transcriptome