Bioactive proteins in healthy pregnancies and preeclampsia: relevance to hypertension and proteinuria.

BACKGROUND: Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. METHODS: Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. RESULTS: Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preeclampsia patients. In particular, interleukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. CONCLUSIONS: Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.

Proteins in leaked amniotic fluid as biomarkers diagnostic for prelabor rupture of membranes.

PURPOSE: Early diagnosis of prelabor rupture of membranes (PROM) is essential to protect mother and fetus from intra-uterus infection and preterm birth. A simple and rapid bedside test would help clinicians confirm the diagnosis for early treatment. EXPERIMENTAL DESIGN: A protein array was used to screen cervical-vaginal fluid (CVF) and amniotic fluid (AF) samples collected from normal and PROM pregnant women. Enzyme-linked immunosorbent assay was used to quantify two novel and potentially useful analytes, soluble intercellular adhesion molecule-1 (sICAM-1) and Axl receptor tyrosine kinase (Axl). RESULTS: The mean concentration of sICAM-1 and Axl was 85 and 482 times higher separately in 30 healthy AF samples than in 110 CVF samples of normal pregnancies. Comparing 110 CVF samples of PROM/Preterm PROM with 110 CVF samples of normal pregnancies, the diagnostic value for PROM was demonstrated by their high sensitivity and specificity (96.4 and 92.7%, respectively, for sICAM-1, and 92.4 and 90.4%, respectively, for Axl). CONCLUSIONS AND CLINICAL RELEVANCE: The results indicate that sICAM-1 and Axl in AF leaked to vagina are sensitive and specific biomarkers for the diagnosis of PROM. Furthermore, sICAM-1 or Axl can be developed into a rapid strip test for bedside use.