Abstract

The potential for developing molecules of interest in preclinical preeclampsia from candidate genes that were discovered on gene expression microarray analysis has been challenged by limited access to additional first trimester trophoblast and decidual tissues. The question of whether these candidates encode secreted proteins that may be detected in maternal circulation early in pregnancy has been investigated using various proteomic methods. Pilot studies utilizing mass spectrometry based proteomic assays, along with enzyme linked immunosorbent assays (ELISAs), and Western immunoblotting in first trimester samples are reported. The novel targeted mass spectrometry methods led to robust multiple reaction monitoring assays. Despite detection of several candidates in early gestation, challenges persist. Future antibody-based studies may lead to a novel multiplex protein panel for screening or detection to prevent or mitigate preeclampsia.

Highlights

  • Preeclampsia continues to be one of three leading causes of maternal mortality worldwide [1]

  • Our long range goals were to develop a multiplex panel for risk screening or preeclampsia detection prior to onset of signs and symptoms

  • We piloted liquid chromatography-tandem mass spectrometry (LC-MS/MS) based multiple reaction monitoring (MRM) assay development to test for protein expression and to quantitate concentrations in maternal serum

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Summary

Introduction

Preeclampsia continues to be one of three leading causes of maternal mortality worldwide [1]. Prediction, prevention, early detection, and personalized treatment of preeclampsia have been stymied by an incomplete understanding of its etiopathogenesis. This genetically complex disorder involves mother, fetus, and their interactions, while at the same time, preeclampsia is multifactorial and seems to consist of various subsets such as early and late onset [5,6]. Around which theories and sub-classifications of preeclampsia revolve is the placenta. The placenta is necessary and sufficient to establish preeclampsia; delivery continues to be the only known cure [7,8]

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