Potential diagnostic value of serum proteome profiling with MALDI-TOF-MS and the suggested serum markers sFlt-1, PlGF and Endoglin in patients with preeclampsia

Background: Release of circulating factors from the placenta that induce endothelial dysfunction is considered as one of the various causes of preeclampsia. A promising approach to biomarker discovery referring to early diagnosis of preeclampsia is protein profiling using matrix assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF-MS). The aim of this study was to evaluate proteome analysis sFlt-1, PlGF and Endoglin to aid early detection and monitoring the course of preeclampsia.

Materials and methods: Serum samples obtained from 29 preeclamptic patients (PE; 27 to 41 week of gestation) and 21 healthy pregnancies with confirmed absence of hypertention, proteinuria or intrauterine growth restriction (HP; 28 to 41 week of gestation) were used to generate high-resolution MALDI-TOF protein profiles. Samples were subjected to prefractionation using WXC surfaces and magnetic beads. Specimen were analysed on a Reflex IV MALDI-TOF using CHCA matrix and collecting 400 satisfactory single spectra, each. Data obtained were analysed with pattern detection algorithms to generate mathematic models with high classification capability. Circulating soluble endoglin, soluble fms-like tyrosine kinase 1 (sFLT1) and placental growth factor (PlGF) were measured in 13 PE-patients and 12 HP-patients, alongside sFLT1:PlGF ratio. In addition correlation with MALDI-TOF was done for these samples. Results: Serum protein profiling results from HP and PE were generated. In comparison to HP a classifying pattern of putative serum markers of PE were found, ranging from 1500 to 6200 Da in mass. A sensitivity of 64.4%, and a specificity of 87.8% for the detection of PE were shown. There was no significant difference comparing early-onset and late-onset PE to gestational age matched controls. sFlt1/PlGF ratio as well as Endoglin was significant increased in PE (n=13) (threshold value for sFlt1/PlGF, PE>47.00, HP<12.02; threshold value for Endoglin, PE>16.00µg/ml, HP<16.00µg/ml). Notably, additional proteome analysis in these patients with quantification of circulating pro- and antiangiogenic proteins did not result in any significant difference in comparison to HP (n=12) (sensitivity 30.00%; specificity 46.67%).

Conclusions: Serum analysis by mass spectrometry MALDI-TOF and pattern profiling is indeed a potential approach to differentiate between preeclampsia and normal gestations. Its possible clinical relevance in preeclampsia requires further studies and is dependent on a considerable number of serum samples.