Kits and methods for prediction and treatment of preeclampsia
Biomarkers tests which can be used to predict a positive or negative risk of preeclampsia are described. More specifically, a panel of biomarkers including MMP-7 and gpIIbIIIa, described. The test is useful to predict preeclampsia when a biological sample is obtained between the 16 th and 22 nd week of pregnancy. Prediction later in pregnancy can be achieved by a combination of Siglec-6, Activin A, ALCAM, and/or FCN2.
1. A method comprising:
obtaining a plasma or serum sample derived from a pregnant human subject in the 8 th to 16 th week of gestation; and
contacting the sample with at least two binding ligands, at least one of which binds biomarker MMP-7 and at least one of which binds biomarker gpIIbIIIa.
2. The method of claim 1 wherein:
the contacting comprises loading samples into:
one or more wells coated with MMP-7 binding ligands and
one or more wells coated with gbIIbIIIa binding ligands.
3. The method of claim 1 , further comprising:
obtaining a second plasma or serum sample derived from the pregnant human subject; and
contacting the second sample with one or more binding ligands that bind a biomarker;
wherein:
(A) the second plasma or serum sample is derived from the pregnant human subject in the 16 th to 22 nd week of gestation; and
the one or more binding ligands comprise:
at least one ligand that binds biomarker MMP-7; and
at least one ligand that binds biomarker gbIIbIIIa; or
(B) the second plasma or serum sample is derived from the pregnant human subject in the 22 nd to 28 th week of gestation; and
the one or more binding ligands comprise:
at least one ligand that binds biomarker Siglec-6; and
at least one ligand that binds biomarker Activin A; or
(C) the second plasma or serum sample is derived from the pregnant human subject in the 28 th to 32 nd week of gestation; and
the one or more binding ligands comprise:
at least one ligand that binds biomarker Siglec-6; and
at least one ligand that binds biomarker ALCAM; and
at least one ligand that binds biomarker FCN2.
4. The method of claim 3 wherein:
when the second sample is obtained between the 16 th to 22 nd week of gestation,
the contacting comprises loading the second sample into:
one or more wells coated with MMP-7 binding ligands; and
one or more wells coated with gbIIbIIIa binding ligands.
5. The method of claim 3 wherein:
when the second sample is obtained between the 22 nd and 28 th week of gestation,
the contacting comprises loading the second sample into:
one or more wells coated with Siglec-6 binding ligands and
one or more wells coated with Activin A binding ligands.
6. The method of claim 3 wherein:
when the second sample is obtained between the 28 th and 32 nd week of gestation,
the contacting comprises loading the second sample into:
one or more wells coated with Siglec-6 binding ligands,
one or more wells coated with ALCAM binding ligands, and
one or more wells coated with FCN2 binding ligands.
7. The method of claim 1 , further comprising:
obtaining a second plasma or serum sample derived from the pregnant human subject in the 16 th to 22 nd week of gestation; and
contacting the second sample with one or more binding ligands that bind a biomarker, wherein the one or more binding ligands comprise:
at least one ligand that binds biomarker MMP-7; and
at least one ligand that binds biomarker gbIIbIIIa; and
obtaining a third plasma or serum sample derived from the pregnant human subject in the 22 nd to 28 th week of gestation; and
contacting the third sample with one or more binding ligands that bind a biomarker, wherein the one or more binding ligands comprise:
at least one ligand that binds biomarker Siglec-6; and
at least one ligand that binds biomarker Activin A; and
obtaining a fourth plasma or serum sample derived from the pregnant human subject in the 28 th to 32 nd week of gestation; and
contacting the fourth sample with one or more binding ligands that bind a biomarker, wherein the one or more binding ligands comprise:
at least one ligand that binds biomarker Siglec-6; and
at least one ligand that binds biomarker ALCAM; and
at least one ligand that binds biomarker FCN2.
8. The method of claim 7 wherein:
for the second sample, the contacting comprises loading samples into:
one or more wells coated with MMP-7 binding ligands; and
one or more wells coated with gbIIbIIIa binding ligands; and
for the third sample, the contacting comprises loading samples into:
one or more wells coated with Siglec-6 binding ligands; and
one or more wells coated with Activin A binding ligands; and
for the fourth sample, the contacting comprises loading samples into:
one or more wells coated with Siglec-6 binding ligands,
one or more wells coated with ALCAM binding ligands, and
one or more wells coated with FCN2 binding ligands.
9. A method comprising:
assaying a serum or plasma sample obtained from a pregnant human subject for expression level of:
biomarker proteins MMP-7 and gbIIbIIIa, and wherein the sample is obtained from the pregnant human subject in the 8 th to 16 th week of gestation.
10. The method of claim 9 wherein:
the assaying comprises loading samples into:
one or more well coated with MMP-7 binding ligands, and
one or more wells coated with gbIIbIIIa binding ligands.
11. The method of claim 9 , further comprising:
assaying a second serum or plasma sample obtained from the pregnant human subject for expression level of:
biomarker proteins MMP-7 and gbIIbIIIa, wherein the second sample is obtained from the pregnant human subject in the 16 th to 21 st week of gestation; and/or
biomarker proteins Siglec-6 and Activin A, wherein the second sample is obtained from the pregnant human subject in the 22 nd to 28 th week of gestation; and/or
biomarker proteins Siglec-6, ALCAM, and FCN2, wherein the second sample is obtained from the pregnant human subject in the 28 th to 32 nd week of gestation.
12. The method of claim 11 wherein:
the second sample is obtained between the 16 th and 21 st week of gestation; and
the assaying comprises loading the second sample into:
one or more wells coated with MMP-7 binding ligands, and
one or more wells coated with gbIIbIIIa binding ligands.
13. The method of claim 11 wherein:
the second sample is obtained between the 22 nd and 28 th week of gestation; and
the assaying comprises loading the second sample into:
one or more wells coated with Siglec-6 binding ligands, and
one or more wells coated with Activin A binding ligands.
14. The method of claim 11 wherein:
the second sample is obtained between the 28 th and 32 nd week of gestation; and
the assaying comprises loading the second sample into:
one or more wells coated with Siglec-6 binding ligands,
one or more wells coated with ALCAM binding ligands, and
one or more wells coated with FCN2 binding ligands.