The development of a peptide SRM-based tandem mass spectrometry assay for prenatal screening of Down syndrome.

Wendy Heywood, Darrell Wang, Tracey E. Madgett, Neil D. Avent, Simon Eaton, Lyn S. Chitty, Kevin Mills*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Two new biomarkers, serum amyloid-P (SAP) and plasma C1-inhibitor protein are elevated in the maternal circulation of mothers carrying Down syndrome foetuses. Much emphasis of late\ has been put on the lack of translational tests being developed following the identification of new biomarkers. We have created a single-reaction-monitoring (SRM) tandem mass spectrometry-based assay for the quantitation of these biomarkers and compared these results with an in-house developed immunofluorescence-based technique (IF). This MS-based assay is a rapid 5 min test and a simple "one pot reaction," requiring only 5μl of plasma. To evaluate the potential of SRM-based quantitation in a clinical setting, SAP and C1-inhibitor were quantitated in 38 normal and Down syndrome affected pregnancies. Plasma SAP levels in the Down's group were significantly raised at 10-14 weeks (p<0.0015) and 14-20 weeks (p<0.0001). Plasma C1-inhibitor levels were also observed significantly elevated in the Down's group (10-14 weeks, p<0.0193, 14-20 weeks, p<0.0001). Analysis using the IF technique did not show any significant elevation of plasma SAP levels or C1-inhibitor levels. This rapid and sensitive assay demonstrates the potential of multiplexed tandem MS-based quantitation of proteins in chemical pathology labs and in a more cost-effective, accurate manner than conventionally used antibody methods.
Original languageEnglish
Pages (from-to)3248-3257
Number of pages0
JournalJ Proteomics
Volume75
Issue number11
DOIs
Publication statusPublished - 18 Jun 2012

Keywords

  • Adult
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Down Syndrome
  • Female
  • Fetus
  • Humans
  • Pregnancy
  • Pregnancy Trimester
  • First
  • Second
  • Prenatal Diagnosis
  • Serum Amyloid P-Component
  • Tandem Mass Spectrometry

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