Neutrophil extracellular traps: The synergy source in the placentae of HIV infected women with pre-eclampsia.

Abstract

To immuno-localize histone H2A expression as a marker of neutrophil extracellular traps (NETs) in the placenta; and to quantify and compare the percentage H2A immune-expression as a marker of NETs in the placental intervillous space according to: pregnancy type, HIV status and across the study population. The participants to the study were a pregnant South African population group of African ancestry (n=60) stratified as normotensive (N) (n=30) or pre-eclamptic (PE) (n=30) and further subdivided as HIV infected (HIV+) (n=15) or HIV naïve (HIV-) (n=15). Following informed consent placental tissue samples were obtained at the time of delivery. Immunohistochemistry using the anti-histone 2A (H2A) antibody as a biomarker of NETs, and morphometric image analysis was used to immuno-localize and quantify placental H2A immuno-expression respectively in the placental inter-villous space. Statistical analysis was performed using Graph Pad Prism software (Version 5). To determine if HIV neutralizes the elevated NETs in PE. NETs were localized within the inter-villous space surrounding the exchange villi and conducting villi of placental tissue. Based on HIV status, a significant elevation in H2A immuno-expression was observed in the HIV+ compared to the HIV- group (p=0.0008) and in the pre-eclampsia HIV- compared to the normotensive HIV- group (p=0.0008). However, a significant decline in H2A immuno-expression was observed in the PEHIV+ group compared to the NHIV+ group (p=0.0072). Both PE and HIV elevate placental NETs; however, they synergistically downregulate NETs expression. Further investigations are required to interrogate the signaling pathways involved to establish potential NET-targeted therapeutic actions.