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

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• 作者：Wendy Heywood^a ; Darrell Wang^a ; Tracey E. Madgett^b ; Neil D. Avent^b ; Simon Eaton^a ; Lyn S. Chitty^a ; ^c ; Kevin Mills^a ; ^{k.mills@ich.ucl.ac.uk}
• 关键词：SRM ; Multiple reaction monitoring ; DS ; Down syndrome ; SAP ; serum amyloid P ; C1-inhibitor ; plasma C1-protease inhibitor ; PLGS ; ProteinLynx Global Server ; ffDNA ; free foetal DNA ; min ; minutes ; h ; hours
• 刊名：Journal of Proteomics
• 出版年：2012
• 期刊代码：P37_18743919
• 类别：ch
• 出版时间：18 June, 2012
• 卷：75
• 期：11
• 页码：3248-3257
• 文件大小：890 K

摘要

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 鈥渙ne pot reaction,鈥?requiring only 5 渭l 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.