Preeclampsia biomarkers and related systems and methods

Abstract

Disclosed herein are methods, kits, tests, and systems for detecting, predicting, monitoring, or ruling out preeclampsia in pregnant women. Also provided herein are novel diagnostic markers, methods of data analysis, assay formats, and kits employing such markers to improve one or more characteristics of a test for identifying or ruling out preeclampsia based on biomarkers from patient samples.

1 . A method for avoiding unnecessary treatment of preeclampsia, the method comprising:
 (a) obtaining a biological sample from a pregnant female subject;   (b) obtaining an amount or concentration of three or more proteins selected from PlGF, sFLT-1, and KIM-1 in the biological sample from the pregnant female subject, wherein the amount or concentration is determined by a process that comprises contacting the biological sample with a plurality of different probes, wherein the plurality of different probes comprises probes with specific affinity for three or more proteins selected from PlGF, sFLT-1, and KIM-1; and   (c) proceeding with treatment of said pregnant human in a manner that avoids unnecessary treatment of preeclampsia based at least in part on the amounts or concentrations of the three or more proteins determined in step (b).   
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the plurality of different probes further comprises probes with specific affinity to fibroblast growth factor 21 (FGF21), and the three or more proteins further comprise FGF21. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the plurality of different probes further comprises probes with specific affinity for cluster of differentiation 274 (CD274), and the three or more proteins further comprise CD274. 
     
     
         9 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the biological sample is obtained from the pregnant female after gestational week 20. 
     
     
         13 . The method of  claim 1 , wherein the biological sample has been collected from the pregnant female prior to gestational week 30. 
     
     
         14 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the biological sample is a urine, blood, amniotic fluid, exosome, plasma, or serum sample. 
     
     
         21 . The method of  claim 1 , wherein the biological sample is from blood of the pregnant human female. 
     
     
         22 . The method of  claim 1 , wherein the amount or concentration of no more than 20 proteins is determined. 
     
     
         23 . The method of  claim 1 , wherein one or more of the plurality of different probes are antibodies or antibody fragments. 
     
     
         24 . The method of  claim 1 , wherein each of the plurality of different probes are antibodies or antibody fragments. 
     
     
         25 - 30 . (canceled) 
     
     
         31 . The method  claim 1 , wherein the biological sample is obtained from the pregnant human while in a perinatologist's office, a labor and delivery room, or triage (ER). 
     
     
         32 . The method of  claim 1 , further comprising separating the biological sample into a plurality of different reaction vessels, the plurality of reaction vessels comprising a first reaction vessel, a second reaction vessel, and a third reaction vessel, wherein contacting the biological sample with the plurality of different probes comprises delivering probes with specific affinity for PlGF in a first reaction vessel, delivering probes with specific affinity to sFlt1 to a second reaction vessel, and delivering probes with specific affinity to KIM1 to a third reaction vessel. 
     
     
         33 . The method of  claim 1 , wherein the step of contacting the biological sample with the plurality of different probes occurs in a single reaction vessel. 
     
     
         34 . The method of  claim 1 , wherein the biological sample was obtained from the pregnant female after the pregnant female has shown one or more symptoms of preeclampsia, wherein the symptoms of preeclampsia are selected from (1) high blood pressure and (2) proteinuria. 
     
     
         35 . The method of  claim 34 , wherein the sample was obtained from the pregnant female after the pregnant female has shown both (1) high blood pressure and (2) proteinuria. 
     
     
         36 . The method of  claim 1 , wherein the plurality of different probes comprises two sets of probes with specific affinity for each of the four or more proteins, wherein each set of the two sets of probes binds to different epitopes. 
     
     
         37 - 154 . (canceled)