Author Response: Identification of Novel Syncytiotrophoblast Membrane Extracellular Vesicles Derived Protein Biomarkers in Early-onset Preeclampsia: A Cross-Sectional Study

Preeclampsia (PE), a multi-systemic hypertensive pregnancy disease that affects 2-8% of pregnancies worldwide, is a leading cause of adverse maternal and fetal outcomes. Current clinical PE tests have a low positive predictive value for PE prediction and diagnosis. The placenta notably releases extracellular vesicles from the syncytiotrophoblast (STB-EV) into the maternal circulation. To identify a difference in placenta and STB-EV proteome between PE and normal pregnancy (NP), which could lead to identifying potential biomarkers and mechanistic insights. Using ex-vivo dual lobe perfusion, we performed mass spectrometry on placental tissue, medium/large and small STB-EVs isolated from PE (n = 6) and NP (n = 6) placentae. Bioinformatically, mass spectrometry was used to identify differentially carried proteins. Western blot was used to validate the identified biomarkers. We finished our investigation with an in-silico prediction of STB-EV mechanistic pathways. We identified a difference in the STB-EVs proteome between PE and NP. Filamin B, collagen 17A1, pappalysin-A2, and scavenger Receptor Class B Type 1) were discovered and verified to have different abundances in PE compared to NP. In silico mechanistic prediction revealed novel mechanistic processes (such as abnormal protein metabolism) that may contribute to the clinical and pathological manifestations of PE. We identified potentially mechanistic pathways and identified differentially carried proteins that may be important in the pathophysiology of PE and are worth investigating because they could be used in future studies of disease mechanisms and as biomarkers. This research was funded by the Medical Research Council (MRC Programme Grant (MR/J0033601) and the Medical & Life Sciences translational fund (BRR00142 HE01.01)