EARLY PREDICTIVE IMMUNOASSAY FOR PREECLAMPSIA

WE WILL DEVELOP A NEW DIAGNOSTIC TEST TO SUBSTANTIALLY IMPROVE THE DEFINITIVE DIAGNOSIS OF PE. PE IS A COMMON DISEASE OF PREGNANT WOMEN AFFECTING THE MOTHER, FETUS, AND NEONATE. PE IS CHARACTERIZED BY THE ONSET OF HYPERTENSION, PROTEINURIA AND EDEMA AFTER THE 20TH WEEK OF GESTATION IN PREVIOUSLY NORMOTENSIVE WOMEN. RECENT STUDIES SUGGEST THAT THE PRIMARY PATHOGENESIS OF THIS DISORDER IS UTEROPLACENTAL PERFUSION INSUFFICIENCY RESULTING IN GENERAL MATERNAL VASCULAR ENDOTHELIAL CELL DAMAGE. ALTHOUGH MORE THAN 100 TESTS HAVE BEEN PUT FORTH AS PREDICTORS OF PE, THERE IS AS YET NO RELIABLE MARKER OF EARLY DETECTION OF PE. WE FIRST EXAMINED PROTEINS THAT WERE KNOWN TO BE SECRETED FROM ENDOTHELIAL CELLS (SUCH AS FIBRONECTIN, ENDOTHELIN 1 AND ICAM 1) AS ELEVATED PLASMA MARKERS IN WOMEN WITH PE. SOME ENDOTHELIAL PROTEINS WERE FOUND TO BE INCREASED IN THE PLASMA IN LATE GESTATION IN WOMEN WITH PE, BUT ELEVATION OF THESE MARKERS DID NOT PRECEDE THE ONSET OF OTHER CLINICAL SYMPTOMS. TO BROADEN THE SCOPE OF PHASE I STUDY INVESTIGATORS EXPANDED THE PANEL OF CLINICAL SPECIMENS UNDER INVESTIGATION TO INCLUDE URINE AS WELL AS SERUM, WITH THE ULTIMATE OBJECTIVE OF DEVELOPING AN NON INVASIVE TEST. MONOCLONAL ANTIBODIES WERE GENERATED AGAINST ANTIGENS IN THE URINE OF WOMEN WITH PE. SEVERAL ANTIBODIES HAVE BEEN IDENTIFIED THAT BIND PE-SPECIFIC URINARY ANTIGENS. THESE ANTIBODIES WERE ABLE TO DIFFERENTIATE PREECLAMPTIC AND NORMOTENSIVE WOMEN IN A PANEL OF 50 PREGNANCIES. PHASE II OF THIS STUDY, WILL BE A PROSPECTIVE CLINICAL TRIAL TO EVALUATE THE DIAGNOSTIC EFFICACY AND COMMERCIAL POTENTIAL OF THESE URINARY ANALYTES AS MARKERS OF PE.