Plasma level of Placental Protein13 (PP13) in Placental-Derived Extracellular Vesicles (PEV) is elevated in patients with preeclamsia but not in preterm delivery and the impact of corticosteroids

Placental extracellular vesicles are delivered to maternal circulation acting as communication vehicles between the placenta and the maternal organs in various physiological and pathological conditions. We aim to determine the level of the immunoregulatory placental protein (PP13) in placental derived extracellular vesicles (pEV) in the maternal circulation in preeclampsia (PE) and preterm delivery (PTD) compared to term normal delivery. The cohort had 20 PE, 16 PTD and 14 matched term control cases. Extracellular vesicles were purified by size exclusion chromatography (SEC), characterized by CD63 and the placental origin of pEVs was verified by placental alkaline phosphatase. ELISA was used to quantify the level of soluble PP13, Its level in pEV and total PP13 determined after the pEV were depleted by plasma treatment by detergent. Using SEC, PP13 was determined on the PEV cargo in addition to its free level in the soluble plasma fraction. Total PP13 was elevated in the PE cases (P<0.01) compared to term normal deliveries, but not compared to PTD. On the isolated EVs, PP13 level was higher mainly in PE<37 weeks (P<0.01). Soluble form of PP13 was not different among the study and control group. Corticosteroid treatment was associated with increased release of PP13 to the plasma for both PE and PTD in either the total fraction or the EV aliquots This is the first study to determine PP13 as a part of the pEV proteome. Its level is increased in PE, which is further augmented among preterm PE treated with corticosteroids.