Introduction: Pre-eclampsia remains one of the leading causing of maternal and perinatal morbidity and mortality. Recent plasma biomarker discovery has improved the diagnosis of pre-eclampsia; however no factors which are quantitatively different remote from disease onset have been identified. Urine represents an ideal non-invasive fluid for analysis and potentially rich source of biomarker detection. Proteomics is a rapidly developing technique which allows the detection and identification of individual proteins. We propose that early glomerular changes will result in significant differences in the urinary proteome of women destined to develop pre-eclampsia, prior to detection of the clinical syndrome.
Objectives: To define a urinary profile at 15 weeks' gestation, predictive of subsequent pre-eclampsia, in low risk nulliparous women.
Methods: Urine samples from twelve women at 15 weeks' gestation who subsequently developed pre-eclampsia (cases) and twelve gestation-, BMI- and age-matched controls were selected from the SCreening Of Pregnancy Endpoints (SCOPE) cohort. A proteome profile was established using a validated workflow, involving selective immunodepletion, 1D SDS-PAGE gel fractionation, in-gel digestion of gel sections, LC-MS/MS analysis and normalised spectral analysis.
Results: More than 900 proteins were identified using minimal stringency in Scaffold. Spectral counts revealed 24 proteins were significantly upregulated in cases and absent in controls and 3 proteins were absent in cases but present in controls. For protection of intellectual property protein identities are omitted.
Conclusions: A urinary proteomic signature can be identified in the urine of women at 15 weeks' gestation who subsequently develop pre-eclampsia. Formal quantitative analysis will be performed with selective reactive-monitoring analysis, followed by subsequent validation of this differential proteomic profile using a larger number samples per groups.
Copyright © 2013. Published by Elsevier B.V.