Biomarkers for hypertensive disorders of pregnancy

Abstract

The application discloses new biomarkers for hypertensive disorders of pregnancy and particularly preeclampsia; methods for the diagnosis, prediction, prognosis and / or monitoring said disorders based on measuring said biomarkers; and kits and devices for measuring said biomarker and / or performing said methods.

Description

RELATED APPLICATIONS[0001]This application claims priority to U.S. provisional application No. 61 / 323,490 filed Apr. 13, 2010 which is incorporated herein by reference.SEQUENCE LISTING[0002]This application includes a sequence listing as an AppendixFIELD OF THE INVENTION[0003]The invention relates to biomarkers, particularly protein- and / or peptide-based biomarkers, useful for the diagnosis, prediction, prognosis and / or monitoring of diseases and conditions in subjects, in particular hypertensive disorders of pregnancy, more in particular preeclampsia; and to related methods, uses, kits and devices.BACKGROUND OF THE INVENTION[0004]In many diseases and conditions, a favourable outcome of prophylactic and / or therapeutic treatments is strongly correlated with early and / or accurate prediction, diagnosis, prognosis and / or monitoring of a disease or condition. Therefore, there exists a continuous need for additional and preferably improved manners for early and / or accurate prediction, dia...

AI Technical Summary

Benefits of technology

[0046]In an embodiment, a method for monitoring a HDP such as preferably PE (or for monitoring the probability of developing a HDP such as preferably PE) comprises the steps of: (i) measuring the quantity of any one or more markers selected from the group consisting of ALS, ADA12, ANGI, CAN1, CSF1R, CRP, CSH, DAG1, DPEP2, DSG2, ECM1, ENPP2, FBLN1, FBN2, GP126, HGFL, ICAM3, KISS1, LCAP, LCAT, PGBM, PGRP2, PHLD, PRDX1, PRDX2, PTPRS, ROBO4, S10A9, SAA4, TENX, TFF3, VGFR3 in samples from a subject from two or more successive time points; (ii) comparing the quantity of the one or more markers between the samples as measured in (i); (iii) finding a deviation or no deviation of the quantity of the one or more markers between the samples as compared in (ii); and (iv) attributing said finding of deviation or no deviation to a change in the HDP (or to a change in the probability of developing the HDP) in the subject between the two or more successive time points. The method thus allows to monitor the HDP or the risk of developing the HDP in a subject over time.

[0047]In another embodiment, a method for monitoring a HDP such as preferably PE (or for monitoring the probability of developing a HDP such as preferably PE) comprises the steps of: (i) measuring the quantity of any two or more markers selected from the group consisting of ALS, ADA12, ANGI, CAN1, CSF1R, CRP, CSH, DAG1, DPEP2, DSG2, ECM1, ENPP2, FBLN1, FBN2, GP126, HGFL, ICAM3, KISS1, LCAP, LCAT, PGBM, PGRP2, PHLD, PRDX1, PRDX2, PTPRS, ROBO4, S10A9, SAA4, TENX, TFF3, VGFR3 in samples from a subject from two or more successive time points; (ii) using the measurements of (i) to establish subject profiles of the quantity of the two or more markers at the two or more successive time points; (iii) comparing the subject profiles as established in (ii); (iv) finding a deviation or no deviation between the subject profiles as compared in (iii); and (v) attributing said finding of deviation or no deviation to a change in the HDP (or to a change in the probability of developing the HDP) in the subject between the two or more successive time points. The method thus allows to monitor the HDP or the risk of developing the HDP in a subject over time.

[0066]Moreover, the present examples show that the biomarkers as taught herein allow to predict a prospective (i.e., future or forthcoming) occurrence of a HDP and preferably PE in pregnant females who, when the biomarkers are being evaluated, do not yet suffer from clinically manifest HDP or PE.

[0127]In a further embodiment, the measuring (and optionally visualisation) means of the portable testing device may comprise a solid support having a proximal and distal end, comprising:—a sample application zone in the vicinity of the proximal end;—a reaction zone distal to the sample application zone; and—a detection zone distal to the reaction zone;—optionally control standards comprising any one or more markers selected from the group consisting of ALS, ADA12, ANGI, CAN1, CSF1R, CRP, CSH, DAG1, DPEP2, DSG2, ECM1, ENPP2, FBLN1, FBN2, GP126, HGFL, ICAM3, KISS1, LCAP, LCAT, PGBM, PGRP2, PHLD, PRDX1, PRDX2, PTPRS, ROBO4, S10A9, SAA4, TENX, TFF3, VGFR3 and / or fragments thereof, whereby said support has a capillary property that directs a flow of fluid sample applied in the application zone in a direction from the proximal end to the distal end; and—optionally comprising a fluid source improving the capillary flow of a more viscous sample.

Problems solved by technology

Hypertensive disorders occurring during pregnancy represent a major cause of maternal morbidity and mortality worldwide, and are also associated with increased perinatal mortality.

However, about 25% of PE tends to be severe, involving symptoms and signs of central nervous system dysfunction, hepatocellular injury, reduced urine output and markedly elevated blood pressure (systolic >160 mmHg or diastolic >110 mmHg).

Severe PE typically occurs in late 2nd and early 3rd trimester and is associated with increased maternal and perinatal morbidity and mortality.

Whereas both these conditions are rare, they are associated with poor prognosis (Solomon & Seely 2006, supra).

Hence, hypertensive disorders of pregnancy and particularly PE remain largely unpredictable in their onset and disease progression.

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