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Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.
Norwitz, Errol R; Tsen, Lawrence C; Park, Joong Shin; Fitzpatrick, Patricia A; Dorfman, David M; Saade, George R; Buhimschi, Catalin S; Buhimschi, Irina A.
Afiliação
  • Norwitz ER; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Am J Obstet Gynecol ; 193(3 Pt 2): 957-64, 2005 Sep.
Article em En | MEDLINE | ID: mdl-16157094
ABSTRACT

OBJECTIVE:

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. STUDY

DESIGN:

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.

RESULTS:

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).

CONCLUSION:

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.
Assuntos
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Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Hemoglobinas Idioma: En Ano de publicação: 2005 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Hemoglobinas Idioma: En Ano de publicação: 2005 Tipo de documento: Article