Methods to diagnose a required regulation of trophoblast invasion

Abstract

Methods are provided for the diagnosis and treatment of patients with increased risk of preeclampsia. The methods involve measuring levels of TGF-β 3 , receptors of cytokines of the TGfβ family, or HIF-1α.

1 . A method for detecting, preventing, and/or treating a condition requiring regulation of trophoblast invasion comprising detecting or modulating TGFβ3, receptors of cytokines of the TGFβ family, HIF-1α, or oxygen tension. 
     
     
         2 . The method according to  claim 1  for diagnosing preeclampsia or an increased risk of preeclampsia in a subject comprising detecting TGF-β 3 , TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α in a sample from the subject. 
     
     
         3 . The method according to  claim 2 , the method comprising:
 (a) collecting a sample from the subject;   (b) measuring the levels of TGF-β 3 , TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α in the sample; and   (c) comparing the levels of TGF-β 3 , TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α in the sample to the levels in women with normal pregnancies or from a sample taken from the subject at a second time of pregnancy.   
     
     
         4 . The method according to  claim 3 , wherein the levels of TGF-β 3 , TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α are measured in a sample from the subject during the first trimester of pregnancy. 
     
     
         5 . The method according to  claim 2 , wherein TGF-β3, TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α are detected using an antibody specific for TGF-β3, TGF-β type I receptor (ALK-I), TGF-β type II receptor (R-II), endoglin, or HIF-1α. 
     
     
         6 . The method according to  claim 2 , wherein TGF-β3, TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II), endoglin, or HIF-1α are detected by measuring a nucleic acid sequence encoding TGF-β3, TGF-β type I receptor (ALK-I), TGF-β type II receptor (R-II), endoglin, or HIF-1α. 
     
     
         7 . The method according to  claim 1  for treating a woman suffering from, or who may be susceptible to preeclampsia, comprising administering a therapeutically effective dosage of an inhibitor of (a) TGF-β 3 , (b) receptors of cytokines of the TGFβ family, or (c) HIF-1α. 
     
     
         8 . The method according to  claim 7 , wherein the inhibitor is antisense to TGFβ 3  or antisense to HIF-1α. 
     
     
         9 . The method according to  claim 7 , wherein the inhibitor is an antibody to TGFβ 3 . 
     
     
         10 . The method according to  claim 7 , wherein the inhibitor is decorin, fetuin, α 2 -macroglobulin, or thyroglobulin, or peptides derived from sites on the compounds that bind to TGFβ3. 
     
     
         11 . A method for evaluating a test substance for its ability to regulate trophoblast invasion comprising the steps of:
 (a) reacting TGFβ 3  and a receptor of a cytokine of the TGFβ family, and a test substance, wherein the TGFβ 3  and receptor of a cytokine of the TGFβ family, are selected so that they bind to form a ligand-receptor complex; and   (b) comparing to a control in the absence of the substance to determine if the substance stimulates or inhibits the binding of TGFβ 3  to the receptor and thereby regulates trophoblast invasion.   
     
     
         12 . A complex comprising receptors selected from the group consisting of TGF-β 3 , TGF-β type I receptor (ALK-I) (RI), TGF-β type II receptor (R-II) and endoglin. 
     
     
         13 . A method of detecting of the complex of  claim 12 , comprising contacting a sample taken from a subject with an antibody that binds to one of the receptors in the complex.