Preeclampsia (PE) is one of the main causes of obstetric complications and leads to both maternal and neonatal mortality. The maternal innate immune system plays an important role throughout pregnancy by providing protection against pathogens, while simultaneously inducing tolerance to a semi-allogenic developing fetus and placental development. Background/Objectives: To conduct a comparative study of immunological markers in the blood and placenta in preeclampsia. Methods: A total of 35 pregnant women were enrolled in a comparative study with preeclampsia (7) and with physiological pregnancy (28). A study of the immune status in peripheral blood and placenta was conducted with an examination of the subpopulation of lymphocytes profile and intracellular cytokines production by flow cytometry. Results: In the blood of pregnant women with PE, there was a decrease in CD14+ monocytes, as well as a significant increase of natural killers CD16+, CD56+ and activation markers HLA-DR+ and CD95+, as well as a significant rise in production of IL-10, TNF, Perforin, GM-CSF, and IGF. At the same time, in placental tissue in patients with preeclampsia, on the contrary, a significant decrease in regulatory cells CD4+, CD8+, CD14+, CD56+, CD59+, activation markers CD95+, as well as anti-inflammatory cytokine IL-10, growth factors VEGFR and IGF was detected. Conclusions: The maternal–fetal immune profile is crucial for successful fetal development and dysregulation of T-, B-, and NK cells can contribute to inflammation, oxidative stress, and the development of preeclampsia.

Background: Recurrent pregnancy loss (RPL) remains etiologically unexplained in 40–50% of cases following standard diagnostic workup. Non-criteria antiphospholipid antibodies (non-criteria aPL) are increasingly considered potential markers of seronegative obstetric antiphospholipid syndrome (APS); however, their diagnostic value in this clinical setting requires further investigation. Objective: To assess the diagnostic value of non-criteria aPL in women with RPL and to construct an exploratory immunological scoring model for diagnostic stratification. Methods: Antiphospholipid antibody detection was performed using a single-measurement semi-quantitative line immunoblot assay (Anti-Phospholipid 10 Dot, Generic Assays, Germany). Statistical analysis included χ², Fisher’s exact test, Mann–Whitney U test, binary logistic regression, and ROC analysis. Results: Statistically significant associations with RPL were observed for anti-prothrombin antibodies (OR = 11.1; 95% CI 1.8–68.0; p = 0.022 [Haldane–Anscombe correction]), anti-annexin V (OR = 4.28; 95% CI 1.18–15.6; p = 0.023), and anti-β₂GP I (OR = 3.31; 95% CI 1.18–9.28; p = 0.019). The exploratory composite immunological score demonstrated moderate discriminatory performance (AUC = 0.701; 95% CI 0.588–0.814; p = 0.005). The overall logistic regression model was statistically significant (χ² = 8.564; p = 0.036), although none of the individual predictors retained independent significance, indicating a contribution of cumulative immunological burden rather than any single marker. Conclusions: In this single-center cross-sectional study, non-criteria aPL were frequently detected in women with RPL and were statistically associated with the condition. The findings should be interpreted as hypothesis-generating only, given the cross-sectional design, single-measurement immunoblot, small control group, and absence of external validation. Confirmation in larger prospective multicenter cohorts using ELISA-based assays with the internationally recommended 12-week repeat measurement is required before any clinical implementation.

Background: Hypertensive conditions during pregnancy, such as preeclampsia (PE), are multisystem obstetric complications, accompanied by changes in the immunological status. Although several types of immune cells are involved in pathogenesis of preeclampsia, such as regulatory T cells, macrophages, natural killer cells, and neutrophils, most studies have focused on the concentration of circulating cytokines. Much less is known about intracellular cytokine production at the level of individual groups of peripheral blood immune cells. This gap limits our understanding of the early immunological changes that precede the clinical manifestation of the disease. Thus, the study of intracellular cytokine production in various leukocyte populations may provide new biomarkers for predicting preeclampsia. Objectives: To test the hypothesis that women with preeclampsia exhibit distinct intracellular cytokine profiles in specific peripheral blood immune cell subsets compared with normotensive pregnant women, and to assess whether these differences could serve as potential biomarkers for disease prediction. Methods: The study included a total of 78 pregnant women admitted to labor with physiological pregnancy (n = 32) and with gestational hypertension (GH) (n = 39) and PE (n = 7). The multicolor immunophenotyping with intracellular cytokine production of TNF, GM-CSF, IGF and receptor VEGFR-2 by different immunocompetent cell types was evaluated on a BD FACS CALIBUR flow cytometer. Results: Flow cytometry revealed a marked increase in the proportion of CD8⁺ GM-CSF⁺, CD56⁺VEGFR2⁺, CD14⁺IL-10⁺, and CD19⁺IGF⁺ cells in both hypertensive groups versus controls (p < 0.001). In contrast, CD56⁺TNF⁺ levels were significantly reduced (p < 0.001). For differentiating PE from GH, CD56+VEGFR2+ and CD19+IGF+ should be prioritized (AUC~0.66–0.78) with good specificity and moderate sensitivity. Conclusions: These data will not only expand existing knowledge about the role of intracellular cytokines in the pathogenesis of preeclampsia, but will also help to obtain new markers for predicting preeclampsia.

Thrombophilia is considered one of the key mechanisms underlying reproductive disorders. Clinical heterogeneity of reproductive disorders and a lack of stratification by phenotype often limit interpretation. Therefore, evaluating thrombophilia-associated genetic markers separately in fetal loss syndrome, postpartum hemorrhage (PPH), and hypertensive disorders of pregnancy is essential. Background/Objectives: To assess the frequency of thrombophilia-related genetic polymorphisms in women with various reproductive disorders and evaluate their association with clinical–anamnestic characteristics and obstetric antiphospholipid syndrome. Methods: A total of 132 women with reproductive disorders (fetal loss syndrome, postpartum hemorrhage, preeclampsia). Results: Statistically significant differences were found when comparing between the groups. Thus, heterozygous F13 genetic polymorphisms were statistically more common in the group with a history of preeclampsia compared to the group with PPH (the G/A genotype was detected in 22.2% versus 10.7%, p = 0.045), and heterozygous ITGA2 gene genetic polymorphisms were also more common (the C/T genotype was detected in 66.7% versus 42.9%, p = 0.023). In women with a history of PPH, homozygous ITGA2 genetic polymorphisms were statistically more common (the T/T genotype was detected 2.6 times more often—21.4% versus 8.8% compared to the group with fetal loss syndrome, p = 0.022; and 3.8 times more often—21.4% versus 5.6% compared to the group with PE, p = 0.022). Conclusions: A study of thrombophilia gene polymorphisms in women with reproductive disorders showed that the G/A genotype of F13, the C/T genotype of ITGA2, and the A/G genotype of MTR:2756 were significantly more common in women with preeclampsia than in the group with postpartum hemorrhage; the T/T genotype of the ITGA2 gene was detected in postpartum hemorrhage. The MTHFR 1286A > C (A/C) polymorphism was associated with a reduced risk of postpartum hemorrhage. In contrast, the MTR 2756A > G (A/G) genotype was associated with an increased risk of preeclampsia.

Background and Objectives: Preeclampsia (PE) and gestational arterial hypertension (GAH) are major hypertensive disorders of pregnancy with overlapping clinical manifestations, which may complicate their differential diagnosis. Circulating microRNAs (miRNAs) are emerging as potential minimally invasive biomarkers reflecting placental dysfunction, hypoxia, impaired trophoblast invasion, angiogenic imbalance, and endothelial dysfunction. This study aimed to evaluate the expression profile of circulating miRNAs in women with PE and GAH and to identify candidate molecular markers capable of differentiating these conditions. Materials and Methods: A case-control study included 101 pregnant women: 39 women with physiologic pregnancy (control group), 23 women with GAH, and 39 women with PE. Plasma levels of 15 candidate miRNAs were quantified using TaqMan-based quantitative reverse-transcription PCR. Results: Twelve of the 15 investigated miRNAs demonstrated significant differences between PE and the control group and between PE and GAH after multiple-testing correction. The most pronounced decrease in PE was observed for miR-210-3p, with a log2 fold-change of −2.06 versus controls and −2.12 versus GAH. In ROC analysis, miR-210-3p showed the highest discriminatory performance for both comparisons, with an area under the curve (AUC) of 0.830 (95% CI, 0.735–0.925) for PE versus controls and 0.823 (95% CI, 0.720–0.925) for PE versus GAH. Other miRNAs, including miR-144-3p, miR-363-3p, miR-29a-3p, and miR-16-5p, also demonstrated moderate-to-good discriminatory performance. Conclusions: PE is characterized by a distinct circulating miRNA profile that differs from both physiologic pregnancy and GAH, whereas the molecular profile of GAH was broadly comparable to that of controls. Among the investigated candidates, miR-210-3p demonstrated the most consistent discriminatory performance and may represent a promising biomarker candidate for differentiating PE from GAH. A combination of several miRNAs may provide greater diagnostic value than individual markers.

Background: Preeclampsia (PE) is a multisystem obstetric complication, accompanied by changes in the immunological status. Immune cells such as regulatory T cells, macrophages, natural killer cells and neutrophils play an important role in the pathogenesis of preeclampsia, but the contribution of other immune cells is now also recognized. Therefore, studying the production of cytokines by different cell types will allow the identification of potential biomarkers for the prediction of preeclampsia. Objectives: to investigate the levels of intracellular cytokine production by lymphocytes of peripheral blood in preeclampsia. Methods: 35 pregnant women admitted to labor with physiological pregnancy (28) and with PE (7). The multicolor immunophenotyping with intracellular cytokine production of TNF, GM-CSF, VEGFR-2, and IGF by different immunocompetent cell types were evaluated on a BD FACS CALIBUR flow cytometer. Results: Women with preeclampsia had a significant increase in the level of CD8+GM-CSF+ cells (28.5 ± 3.7 vs. 17.3 ± 1.5 in the control group, p<0.001), and CD56+VEGF2+ (14.2±3.47 vs 0.62±0.55, p<0.001), and CD14+IL-10+ cells (55.7 ± 15.7 vs. 0.89 ± 0.61 in the control group, p<0.001), and level of CD19+IGF+ (12.0 ± 3.99 vs 1.10±0.46 in the control group, p<0.001). In contrast, the content of CD56+TNF+ cells was significantly reduced in the PE group compared to the control group (2.26 ± 1.15 vs. 15.7 ± 1.74, p<0.001). Conclusions: These data will not only expand existing knowledge about the role of intracellular cytokines in the pathogenesis of preeclampsia, but will also help to obtain new markers for predicting preeclampsia.