Methods of diagnosing pre-eclampsia or eclampsia
AssigneeBeth Israel Deaconess Medical Center, Inc.
InventorsS. Ananth Karumanchi, Sharon Maynard, Vikas P. Sukhatme
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Abstract
Disclosed herein are methods for diagnosing pre-eclampsia and eclampsia. Also disclosed herein are methods for treating pre-eclampsia and eclampsia using compounds that increase VEGF or PlGF levels or compounds that decrease sFlt-1 levels. Compounds that inhibit the binding of VEGF or PlGF to sFlt1—are also disclosed herein for the treatment of pre-eclampsia or eclampsia.
Claims45
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the level of soluble Flt-1 receptor (sFlt-1) polypeptide in a sample from said subject, wherein a level of sFlt-1 polypeptide greater than 2 ng/ml diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the level of free placental growth factor (PlGF) polypeptide in a serum sample from said subject, wherein said free PlGF is a PlGF polypeptide that has the ability to bind to sFlt-1, and wherein said subject is pregnant and a level of free PlGF polypeptide less than 150 pg/ml serum at 13-16 weeks of pregnancy diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the level of free vascular endothelial growth factor polypeptide in a sample from said subject, wherein said free VEGF is a VEGF polypeptide that has the ability to bind to sFlt-1, and wherein said subject is pregnant and a level of free VEGF polypeptide less than 5 pg/ml serum diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the levels of at least two of sFlt-1, free VEGF, and free PlGF polypeptide in a sample from said subject, wherein said free VEGF is a VEGF polypeptide that has the ability to bind to sFlt-1 and wherein said free PlGF polypeptide is a polypeptide that has the ability to bind to sFlt-1, and comparing the level to the level of at least two of sFlt-1, free VEGF, or free PlGF polypeptide in a reference, and wherein an increase of at least 10% in the level of sFlt-1 or a decrease of at least 10% in the level of free VEGF or free PlGF polypeptide relative to said reference diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising:
- (a) measuring the levels of sFlt-1, free VEGF, and free PlGF polypeptides in a sample from a subject, wherein said free VEGF is a VEGF polypeptide that has the ability to bind to sFlt-1 and wherein said free PlGF polypeptide is a polypeptide that has the ability to bind sFlt-1;
- and
- (b) calculating the relationship between said levels of sFlt-1, free VEGF, and free PlGF using a metric, wherein said metric comprises a pre-eclampsia anti-angiogenic index (PAAI):[sFlt-1/free VEGF+ free PlGF], and wherein a PAAI value greater than 20 in the subject sample diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the level of at least one of sFlt-1, free VEGF, or free PlGF polypeptide in a sample from a subject, wherein said free VEGF is a VEGF polypeptide that has the ability to bind to sFlt-1 and wherein said free PlGF polypeptide is a polypeptide that has the ability to bind sFlt-1, and comparing the level to the level of sFlt-1, free VEGF, or free PlGF polypeptide in a reference, and wherein an increase of at least 10% in the level of sFlt-1 or a decrease of at least 10% in the level of free VEGF or free PlGF polypeptide relative to said reference diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
A method of diagnosing a human pregnant subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, said method comprising measuring the level of free PlGF polypeptide in a serum sample from said subject and the level of sFlt-1 in a bodily fluid sample from said subject, wherein said free PlGF is a polypeptide that has the ability to bind to sFlt-1, and wherein a level of free PlGF polypeptide less than 400 pg/ml serum at mid-gestation and wherein a level of sFlt-1 polypeptide greater than 2 ng/ml diagnoses said subject as having, or having a propensity to develop, pre-eclampsia or eclampsia.
Dependencies are inferred from the claim text.