478: Inflammatory gene expression in placentas of pregnancies with Intra-Amniotic Infection (IAI) and Severe Preeclampsia (sPE)

Abstract

A causal link between aberrant placental inflammatory function, IAI and sPE has been established, though the clinical phenotypes of these two conditions differ. Moreover, anti-inflammatory prophylactic therapies (i.e. aspirin) have been proposed for sPE, although the mechanism through which this drug may act is a subject of debate. We sought to compare and contrast the gene expression signatures for inflammatory pathways in placentas from pregnancies complicated by IAI versus sPE. RNA was extracted from placental tissue from singleton pregnancies with unambiguous clinical phenotypes: 1) amniocentesis-proven IAI (n=5, GA: 27±2 wks); 2) early-onset sPE (n=8, GA: 30±1 wks); and 3) idiopathic preterm birth (iPTB, n=5, GA: 32±1wks). All subjects received antenatal corticosteroids, but no aspirin, prior to delivery. There was no difference in GA at delivery among groups. RNA-sequencing was performed on Illumina platform and data analyzed using 'edgeR'. Differentially expressed genes (DEG, FDR < 0.1) mapped to the Immune Response Gene Ontology Pathway (GO:0006955) were annotated and subjected to overrepresentation and protein-protein-interaction (PPI) analyses. The number of DEG in sPE and IAI placenta compared to iPTB placenta is presented in Fig. A. Of these, immune response genes were 32 in IAI and 55 in sPE (Fig. B). Only one gene, the tyrosine-protein kinase KIT or CD117, was common to both conditions. Pathway analysis revealed that IAI was associated with a transcriptional signature enriched for myeloid cell responses, TLR-signaling, and transcripts encoding extracellular proteins (Fig C). In contrast, sPE showed overrepresentation for T and B lymphocyte signaling pathways, AGE-RAGE signaling, and transcripts coding for cell surface receptor molecules (Fig D). While placental inflammation represents an important pathogenic component both in IAI and sPE, the specific gene expression signatures associated with immune dysregulation are markedly different. This data could help with effective repurposing of known anti-inflammatory drugs for sPE or spontaneous PTB.