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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. Blood samples were collected from 214 women in the following groups: (1) normal pregnancy sampled &lt;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. (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. 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.

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