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PM.11 A Label-Free SRM Workflow Identifies a Subset of Pregnancy Specific Glycoproteins as Novel Predictive Markers of Early-Onset Pre-Eclampsia
  1. RT Blankley1,
  2. C Fisher1,
  3. M Westwood1,
  4. RA North4,
  5. Baker Philip1,2,
  6. M Walker1,
  7. T Whetton1,
  8. L McCowan2,
  9. G Dekker3,
  10. R Unwin1,
  11. JE Myers1
  1. 1University of Manchester, Manchester, UK
  2. 2University of Auckland, Auckland, New Zealand
  3. 3University of Adelaide, Australia, Australia
  4. 4Kings College London, London, UK


Objective The aim of this study was to identify and verify plasma protein markers which may add to predictive algorithms for pre-eclampsia (PE) in asymptomatic nulliparous women.

Methods We used a quantitative mass spectrometry (MS) approach to identify proteins with abundance changes in plasma (15 weeks) taken from women who subsequently develop PE recruited to the international SCOPE study. We developed a novel, targeted, label-free MS method, selective reaction monitoring (SRM) which enabled robust and reproducible verification of these proteins in a further 100 samples (16 early-onset PE, 42 late-onset PE, 42 controls).

Results We identified and quantified >500 plasma proteins, and prioritised a set of candidate predictive markers. The two most promising, Platelet Basic Protein (PBP/NAP-2) and Pregnancy-specific glycoprotein (PSG)-9 were selected for further verification. The SRM method was validated extensively using dilution experiments for PSG proteins and by comparison to a commercial ELISA for NAP-2. NAP-2 was only elevated in a subset of women with PE, however, peptides unique to PSG-9 and PSG-5 were consistently elevated in women with subsequent early onset PE (p < 0.01; AUCs 0.72–0.75). Other PSG peptides were not different between groups.

Conclusion This study has identified specific PSG proteins as being predictive of early-onset PE. Importantly, use of a highly specific MS method has enabled measurement of individual PSG family members which has not been possible using antibody-based techniques. Future work is needed to determine whether these proteins will improve current prediction algorithms for the identification of PE in low risk nulliparous women.

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