The programmed cell death protein 1 (PD-1) receptor has been reported to downregulate T cell activation effectively via binding to its ligands PD-L1 or PD-L2 in a negative co-stimulatory manner. Little is known about the involvement of PD-1 mediated immunoregulation in pregnancy and in pregnancy-related disorders. In this work, we investigated the possible role of the PD-1 co-stimulatory pathway in the pathogenesis of the clinical phase of early-onset preeclampsia characterized by a systemic maternal inflammatory response. We performed a cross-sectional study for comparative analysis of phenotypic and functional characteristics of peripheral blood mononuclear cells in women with early-onset preeclampsia and third-trimester healthy pregnant controls. According to our findings, enhanced expression of either PD-1 or its ligand PD-L1, or both, on the cell surface of effector cells (T cells, natural killer (NK) cells, natural killer T (NKT)-like cells) and Tregs could be observed, but PD-1 expression did not correlate with effector cells exhaustion. These results suggest the failure of the axis to downregulate Th1 responses, contributing thereby to the exaggerated immunoactivation observed in early-onset preeclampsia.

Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface.

During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence coupled with the extreme extent regarding the volume expansion, are likely accompanied with pathological conditions. Undoubtedly, preeclampsia, defined as the appearance of hypertension and organ deficiency, such as proteinuria during the second half of pregnancy, is not a homogenous disease. Clinically speaking, two main types of preeclampsia can be distinguished, in which a marked difference between them is vascular condition, and consequently, the blood volume. The "classic" preeclampsia, as a two-phase disease, described in the first, latent phase, in which, placenta development is diminished. Agents from this malperfused placenta generate a maternal disease, the second phase, in which endothelial damage leads to hypertension and organ damage due to vasoconstriction and thrombotic microangiopathy. In this hypovolemia-associated condition, decreasing platelet count, signs of hemolysis, renal and liver involvement are characteristic findings; proteinuria is marked and increasing. In the terminal phase, visible edema develops due to increasing capillary transparency, augmenting end-organ damages. "Classic" preeclampsia is a severe and quickly progressing condition with placental insufficiency and consequent fetal growth restriction and oligohydramnios. The outcome of this condition often leads to fetal hypoxia, eclampsia or placental abruption. The management is limited to a diligent prolongation of pregnancy to accomplish improved neonatal pulmonary function, careful diminishing high blood pressure, and delivery induction in due time. The other subtype, associated with relaxed vasculature and high cardiac output, is a maternal disease, in which obesity is an important risk factor since predisposes to enhanced water retention, hypertension, and a weakened endothelial dysfunction. Initially, enhanced water retention leads to lowered extremity edema, which oftentimes progresses to a generalized form and hypertension. In several cases, proteinuria appears most likely due to tissue edema. This condition already fully meets preeclampsia criteria. Laboratory alterations, including proteinuria, are modest and platelet count remains within the normal range. Fetal weight is also normal or frequently over average due to enhanced placental blood supply. It is very likely, further water retention leads to venous congestion, a parenchyma stasis, responsible for ascites, eclampsia, or placental abruption. During the management of this hypervolemia-associated preeclampsia, the administration of diuretic furosemide treatment seemingly offers promise.

Összefoglaló. Egészséges terhességben mintegy két literrel nő a vér mennyisége. A vérvolumen növekedésének elmaradása, de extrém mértékű növekedése is súlyos következményekkel szövődhet. Ma már nem kétséges, hogy a praeeclampsia, mely a várandósság második felében magas vérnyomás és proteinuria együttes megjelenése, nem egységes kórkép. A korai kezdetű (34. hét előtt jelentkező), hypovolaemiával járó praeeclampsia placentaris eredetű, melyben az endothelium sérülése vezet a magas vérnyomásért és szervkárosodásokért felelős vasoconstrictióhoz és microthrombosisok megjelenéséhez. Magzati sorvadás, oligohydramnion alakul ki a lepényi elégtelenség miatt. A kórkép végső stádiumában magzati elhalás, eclampsia, lepényleválás várható. Az állapot kezelésében rendkívül korlátozottak a lehetőségek; a cél, körültekintő monitorizálás és az állapot stabilizálása mellett, várakozás a magzati tüdő érettségének fokozódása érdekében. A késői kezdetű, nagy perctérfogattal járó praeeclampsia anyai betegség: ebben az obesitasnak kockázati szerepe van, mivel önmagában is hajlamosít fokozott folyadék-visszatartásra, magas vérnyomásra és mérsékelt endothelkárosodásra. A kezdeti lábszár-, majd generalizálódó oedema mellett nemritkán jelentkezik magas vérnyomás és az esetek egy részében proteinuria is, mely ekkor már megfelel a praeeclampsia kritériumának. A magzat súlya normális vagy átlag feletti. Az extrém fokú folyadékretenció, valószínűleg a parenchymalis pangás miatt, asciteshez, eclampsiához, lepényleváláshoz vezethet. A hypervolaemiával járó praeeclampsia kezelésében a diuretikus furoszemidkezelés ígéretesnek tűnik. Orv Hetil. 2022; 163(17): 663–669. Summary. During normal pregnancy, blood volume increases by nearly two liters. Distinctively, the absence and also the extreme extent regarding the volume expansion are likely accompanied with serious conditions. Undoubtedly, preeclampsia, defined as the appearance of hypertension and proteinuria during the second half of pregnancy, is not a homogenous disease. The early onset which begins prior to the 34th week, is characteristically a hypovolemia-associated form and depicts the placental origination, in which endothelial damage leads to hypertension and organ damage due to vasoconstriction and microthrombosis. Fetal blood supply progressively worsens due to placental insufficiency. The outcome of this condition often leads to fetal death, eclampsia, or placental abruption. Management is confined to a diligent prolongation of pregnancy to accomplish improved neonatal pulmonary function. The late onset form, associated with high cardiac output, is a maternal disease, in which obesity is a risk factor since it predisposes individuals to enhanced water retention, hypertension, and a weakened endothelial dysfunction. Initially, low extremity edema oftentimes progresses to a generalized form and frequently results in hypertension. In several cases proteinuria appears. This condition entirely meets the preeclampsia criteria. Fetal weight is normal or frequently over the average. It is very likely, the increasing parenchymal stasis will lead to ascites, eclampsia, or placental abruption. During the management of this hypervolemia-associated preeclampsia, the administration of diuretic furosemide treatment seemingly offers promise. Orv Hetil. 2022; 163(17): 663–669.