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

• Published in: Journal of proteomics 2012-06, Vol.75 (11), p.3248-3257
• Main Authors: Heywood, Wendy, Wang, Darrell, Madgett, Tracey E., Avent, Neil D., Eaton, Simon, Chitty, Lyn S., Mills, Kevin
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome aberrations; Diverse techniques; Down syndrome; Fundamental and applied biological sciences. Psychology; Medical genetics; Medical sciences; Molecular and cellular biology; Multiple reaction monitoring; Plasma C1-protease inhibitor; Prenatal screening; Serum amyloid P; Tandem mass spectrometry
• ISSN: 1874-3919
• DOI: 10.1016/j.jprot.2012.03.037

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 5min 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 10–14weeks (p