Cryodetector mass spectrometry profiling of plasma samples for HELLP diagnosis: An exploratory study

Abstract

The cryodetector MS-based screening method enables the rapid and reliable separation of hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) patients from healthy women. For developing the assay, plasma protein abundances from patients suffering from HELLP were profiled before and after delivery and compared to healthy pregnant and nonpregnant control individuals, using a TOF mass spectrometer equipped with a cryodetector system. The spectra were well reproducible when acquisition conditions were kept constant and the overall appearance of the profiles was well comparable. Peak areas of ten selected ion signals (9.5, 11.8, 14.0, 28.1, 43.4, 50.5, 60.1, 66.6, 74.5, and 79.8 kDa) from each spectrum were subjected to statistical analysis. Significant differences in ion intensities between the groups could be measured even without sample fractionation. The most striking difference between most of the spectra from HELLP patients and nonHELLP samples was the presence/absence of the 11.8 kDa ion signal (p-value: 0.0000365), most likely belonging to serum amyloid A (SAA). Other significant differences in ion intensities between HELLP and control samples were observed in the peak areas of the 14.0, 28.1, 50.5, and 74.5 kDa ion signals. Using the cryodetector MS data for sorting plasma samples into either the HELLP group (n = 8) or the nonHELLP group (n = 22), a sensitivity of 87.5% and a specificity of 100% were achieved. The positive predictive value of our screening assay was 100% and a negative predictive value of 95.6% was obtained with the samples included in this study.