Article

Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
American Journal of Obstetrics and Gynecology (impact factor: 3.47). 10/2005; 193(3 Pt 2):957-64. DOI:10.1016/j.ajog.2005.06.055
Source: PubMed

ABSTRACT Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity.
CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score.
PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001).
Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.

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Keywords

applying Mass Restricted analysis
 
biomarkers composing
 
clinically
 
CSF leukocyte counts
 
discriminative proteomic biomarker profile
 
discriminatory protein peaks
 
free hemoglobin
 
idiopathic multisystem disorder specific
 
In-gel tryptic digests
 
individual CSF SELDI tracings
 
magnesium seizure prophylaxis
 
on-chip immunoassays
 
physiologic implications
 
PPB median [range]
 
PPB score distinguished patients
 
Preeclampsia Proteomic Biomarker
 
protein biomarkers characteristic
 
Proteomic identification techniques
 
surface-enhanced laser desorption/ionization time-of-flight
 
Western blot analysis