Two blood-based biomarkers were strongly associated with risk for preeclampsia in a small study of pregnant women published July 3 in the Journal of Clinical Endocrinology and Metabolism. This discovery may create opportunities for the development of diagnostics and therapies, researchers reported.
The proof-of-concept study looked at the levels and ratio of the proteins FK506-binding protein like (FKBPL) and cluster of differentiation 44 (CD44) in plasma of pregnant women and matched normal controls at the Royal Jubilee Maternity Hospital in Belfast, U.K., and how they associated with risk for preeclampsia.
A high plasma CD44/FKBPL ratio at 20 weeks' gestation was independently associated with a 2.5-fold increased risk of preeclampsia, a statistically significant result, Lana McClements, PhD, a lecturer at the University of Technology Sydney, and colleagues reported. Furthermore, when they incorporated high arterial blood pressure along with the CD44/FKBPL ratio at 20 weeks' gestation, the researchers found that the risk was 3.9-fold higher.
Some biomarkers are currently in use for the condition, but these are mainly used for early-onset preeclampsia (gestation earlier than 34 weeks) and risk stratification strategies are lacking for late-onset preeclampsia (34 weeks-plus), the authors wrote. The ratio correlated with development of late-onset preeclampsia, which accounts for the majority of cases.
"This is particularly important as stratifying pregnancies at risk of preeclampsia has been associated with improved pregnancy outcomes and appears cost-effective, even a few weeks before the clinical onset of disease," McClements et al wrote.
A dangerous condition
The study was funded by a research grant from Invest Northern Ireland, an economic development agency. The researchers noted that there is great interest in the development of new biomarkers for preeclampsia, as it is a common and dangerous hypertensive condition, occurring in 2% to 8% of pregnancies.
Changes in the angiogenic balance during pregnancy have been linked to preeclampsia. Angiogenesis may be measured through soluble fms-like receptor tyrosine kinase-1 (sFlt-1) and placental growth factor (PIGF) testing, but this only helps predict the condition a few weeks before clinically obvious symptoms are evident, the authors noted. FKBPL has potent antiangiogenic activity and "plays an important role in both developmental and pathological angiogenesis," the authors noted.
"Inhibition of angiogenesis and stem cell [signaling] by FKBPL appears to be dependent on CD44," McClements and colleagues wrote. "As a critical inhibitor of angiogenesis, we [hypothesized] that the FKBPL-CD44 pathway has an important role in the pathogenesis of preeclampsia, which could be [utilized] for diagnostic and therapeutic purposes."
For the study, plasma was analyzed using an enzyme-linked immunosorbent assay (ELISA) in women, including patients diagnosed with preeclampsia and those at risk for it, plus healthy matched controls.
"Plasma FKBPL concentration was reduced at both 15 and 20 weeks' gestation whereas plasma CD44 concentration was increased at 20 weeks' gestation in a low-risk cohort of women who proceeded to develop preeclampsia," the authors explained. "High CD44 and low FKBPL are likely driven by hypoxia, which is a pro-angiogenic stimulus as a result of potential compensatory angiogenesis early in pregnancy."
Awareness of the risk for preeclampsia could open up therapeutic options -- for example, emerging mesenchymal stem cell treatments, the authors suggested. Mesenchymal stem cells have been shown to restore angiogenic balance in preclinical studies and have potential to restore FKBPL levels to normal, "potentially improving the vascular response and symptoms of preeclampsia," though research is still in early stages.
"The plasma CD44/FKBPL ratio could provide a novel risk stratification approach for preeclampsia at 20 weeks' gestation, capable of identifying women at high risk, who otherwise appear healthy," the authors concluded.
McClements and co-author Tracy Robson, PhD, of the Irish Centre for Vascular Biology, hold a patent on the FKBPL protein and another patent related to the CD44/FKBPL ratio has been filed. McClements told LabPulse.com that the researchers are interested in commercialization opportunities and are speaking to a number of companies regarding validation and development of the biomarkers into a new test for prediction and diagnosis of preeclampsia.