DYNAMIC OF SFLT-1 OR ENDOGLiN/PIGF RATIO AS AN INDICATOR FOR IMMINENT PREECLAMPSIA AND/OR HELLP SYNDROME

Abstract

Diagnostic methods and tools relating to diagnosing whether a pregnant subject is at risk for developing preeclampsia and/or early-onset preeclampsia within a short period of time. The methods include determining the amounts of the biomarkers sFlt-1 or Endoglin and PIGF in a first and a second sample of said subject, said first sample being obtained prior to said second sample; calculating a first ratio from the amounts of sFlt-1 or Endoglin and PIGF determined in the first sample, and a second ratio from the amounts of sFlt-1 or Endoglin and PIGF determined in the second sample; and comparing the value of the first and the second ratio, whereby a subject being at risk for developing preeclampsia within a short period of time is diagnosed if the value of the second ratio is increased compared to the value of the first ratio by a factor of at least about 3.

What is claimed is: 
     
         1 . A method for diagnosing and treating a pregnant subject being at risk of developing early onset preeclampsia comprising:
 a) measuring amounts of a first biomarker selected from the group consisting of sFlt-1 and endoglin and a second biomarker being PIGF in a first and a second sample of said subject, wherein said first sample has been obtained less than 4 weeks prior to said second sample, the second sample is obtained no later than week 30 of gestation, and wherein said first and second sample are independently selected from the group consisting of a blood sample, a serum sample and a plasma sample;   b) determining a first ratio from said amounts of sFlt-1 to PIGF or Endoglin to PIGF measured in the first sample and a second ratio from said amounts of sFlt-1 to PIGF or Endoglin to PIGF determined in the second sample;   c) diagnosing the subject as being at risk for developing early onset preeclampsia if the value of the second ratio is at least 3 times the value of the first ratio; and   d) providing at least one supportive measure to a subject diagnosed as being at risk for developing preeclampsia within about 16 days.   
     
     
         2 . The method of  claim 1 , wherein said pregnant subject is between about week 15 and no later than week 30 of gestation. 
     
     
         3 . The method of  claim 1 , wherein at least one supportive measure is selected from the group consisting of: close monitoring, hospitalization, administration of blood pressure reducing agents, life style recommendations, and combinations thereof. 
     
     
         4 . A method for diagnosing whether a pregnant subject is at risk for developing preeclampsia within a short period of time comprising:
 a) measuring amounts of a first biomarker selected from the group consisting of sFlt-1 and Endoglin and a second biomarker being PIGF in a first and second sample of said subject, wherein said first sample has been obtained less than 4 weeks prior to said second sample, the second sample is obtained no later than week 30 of gestation, and wherein said first and second sample are independently selected from the group consisting of a blood sample, a serum sample and a plasma sample, wherein the amounts of first biomarker are measured by:
 contacting a portion of the first sample obtained from said subject with an antibody having specific binding affinity for sFlt-1 or Endoglin, thereby forming a complex between the antibody and sFlt-1 or Endoglobin, wherein the antibody having specific bind affinity for sFl-1 comprises two monoclonal antibodies, wherein the first monoclonal antibody is biotinylated, and wherein the antibody having specific binding affinity for Endoglin is a monoclonal antibody; 
 separating the complex formed in said step of contacting from antibody not comprising the complex; and 
 quantifying a signal from the complex, the signal being proportional to the concentration of sFlt-1 or Endoglin in the sample obtained from the subject, 
 wherein the amounts of the second are measured as follows: 
 contacting a portion of the first sample and the second sample obtained from said subject with an antibody having specific binding affinity for PIGF, thereby forming a complex between the antibody and PIGF; 
 separating the complex formed in said step of contacting from antibody not comprising the complex; and 
 quantifying a signal form the complex, the signal being proportional to the concentration of PIGF in the sample obtained from the subject; 
   b) measuring a first ratio from said amounts of sFlt-1 to PIGF or Endoglin to PIGF determined in the first sample and a second ratio from said amounts of sFlt-1 to PIGF or Endoglin to PIGF determined in the first sample and a second ratio from said amounts of sFlt-1 to PIGF or Endoglin to PIGF measured in the second sample; and c) diagnosing the subject as being at risk for developing preeclampsia within a short period of time, wherein the short period of time is about 16 days, if the value of the second ratio is at least 3 times the value of the first ratio; and d) providing at least one supportive measure to the subject.   
     
     
         5 . The method of  claim 4 , wherein said preeclampsia is early onset preeclampsia. 
     
     
         6 . The method of  claim 4  further comprising at least one supportive measure to the subject. 
     
     
         7 . The method of  claim 6 , wherein at least one supportive measure is selected from the group consisting of: close monitoring, hospitalization, administration of blood pressure reducing agents, life style recommendations, and combinations thereof.