Maternal circulating concentrations of soluble Fas and Elabela in early- and late-onset preeclampsia

Abstract

Objective

The Fas/Fas ligand (FASL) system and Elabela-apelin receptor signaling pathways are implicated in the pathophysiology of preeclampsia. The aim of the current study was to investigate whether a model combining the measurement of sFas and Elabela in the maternal circulation may serve as a clinical biomarker for early- and/or late-onset preeclampsia more effectively than measures of each biomarker individually.

Methods

Blood samples were collected from 214 women in the following groups: (1) normal pregnancy sampled <34 weeks of gestation (n = 56); (2) patients who developed early-onset preeclampsia (n = 54); (3) normal pregnancy sampled ≥34 weeks of gestation (n = 52); (4) patients who developed late-onset preeclampsia (n = 52). Maternal circulating soluble Fas and Elabela concentrations were determined using sensitive and validated immunoassays. Two sample t-tests, multivariate logistic regression, and receiver operating characteristic curves were used for analyses.

Results

(1) Women with early-onset preeclampsia, and those with late-onset preeclampsia with placental lesions of maternal vascular malperfusion, had increased concentrations of sFas compared to their gestational age-matched normal controls; (2) women with late-onset preeclampsia, but not those with early-onset preeclampsia, had increased concentrations of Elabela compared to their gestational age-matched counterparts; and (3) an increase in both Elabela and sFas concentrations was more strongly associated with late-onset preeclampsia than early-onset preeclampsia relative to models including either of the markers alone.

Conclusions

A combined model of maternal sFas and Elabela concentrations provides a stronger association with late-onset preeclampsia than either protein alone. This finding demonstrates the possibility to improve the classification of late-onset preeclampsia by combining the results of both molecular biomarkers.

Keywords:

• Apela
• biomarker
• maternal vascular underperfusion
• placenta lesions
• pregnancy
• preterm delivery

Acknowledgements

We gratefully acknowledge the PRB Translational Research Laboratory (Rona Wang) for their contributions to the execution of this study. We thank the physicians and nurses from the Center for Advanced Obstetrical Care and Research and the Intrapartum Unit for their help in collecting human samples. We also thank staff members of the PRB Clinical Laboratory and the PRB Histology/Pathology Unit for the processing and examination of the pathological sections.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. [HHSN275201300006C]. Dr. Romero has contributed to this work as part of his official duties as an employee of the United States Federal Government. N. G.-L. was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.