Diagnosis and treatment of preeclampsia
Disclosed are biomarkers for preeclampsia including elevated levels of free hemoglobin, including free fetal haemoglobin and the ratio of free fetal hemoglobin to total free hemoglobin. Also disclosed are methods of treating preeclampsia using a therapeutic agent that reduces free circulating hemoglobin levels.
1. A method of treating preeclampsia in a pregnant female subject in need thereof, comprising administering to the subject an effective amount of one or more therapeutic agents that reduce free circulating hemoglobin levels.
2. The method of claim 1 , wherein the one or more agents are selected from hemoglobin-binding agents, heme-binding agents, hemoglobin-degrading agents, heme-degrading agents, and iron-binding agents.
3. The method of claim 1 , wherein the one or more therapeutic agents are selected from hemoglobin-binding antibodies or fragments thereof, haptoglobulin, CD163, alpha-1-microglobulin, hemopexin, heme-oxygenase, albumin, transferrin, and ferritin.
4. The method of claim 1 , wherein the subject is at a gestational age of at least 12 weeks.
5. The method of claim 1 , The method of any one of the preceding claims, wherein the subject is at a gestational age of from 12 to 20 weeks.
6. The method of claim 1 , wherein the subject does not exhibit clinical signs of preeclamsia at the time of treatment.
7. The method of claim 1 , wherein the subject in need thereof has a higher level of free fetal hemoglobin or a higher ratio of free fetal hemoglobin to total free hemoglobin than a control.
8. The method of claim 7 , further comprising, prior to said administering, measuring free fetal hemoglobin in a biological sample from a pregnant female subject, and, optionally, measuring total free hemoglobin in a biological sample from the subject.
9. The method of claim 1 , further comprising, prior to said administering:
measuring free fetal hemoglobin in a biological sample from a pregnant female subject,
optionally, measuring total free hemoglobin in a biological sample from the subject,
selecting the subject as a subject in need of treatment for preeclampsia when the subject has a higher level of free fetal hemoglobin than a control, or, optionally, when the subject has a higher ratio of free fetal hemoglobin to total free hemoglobin than a control.
10. The method of claim 8 , wherein the biological sample is selected from blood, blood serum, plasma, urine, and vaginal secretions.
11. The method of claim 8 , wherein detecting free fetal hemoglobin comprises contacting a sample of biological fluid from the subject with an antibody or antibody fragment that specifically binds to fetal hemoglobin (hemoglobin F).
12. The method of claim 8 , wherein detecting free fetal hemoglobin comprises contacting a sample of biological fluid from the subject with an antibody or antibody fragment that specifically binds to the gamma chain of fetal hemoglobin (Hbγ).
13. The method of claim 8 , wherein total free hemoglobin is measured by measuring a level of HbA, HbA2, and HbF.
14. The method of claim 8 , wherein total free hemoglobin is measured by measuring a level of Hbα.
15. The method of claim 8 , wherein total free hemoglobin is measured by measuring by a level of Hbα, Hbβ, Hbα, and Hbγ.