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.

Early-onset preeclampsia is a common obstetrical disease with a potential genetic background and is characterized by the predominance of Th1 immune response. However, although many studies investigated the immunological environment in preeclamptic patients, no information is available about the potential role of the TIGIT/CD226/CD112/CD155 immune checkpoint pathway. A total of 37 pregnant women diagnosed with early-onset preeclampsia and 36 control women with appropriately matched gestational age were enrolled in this study. From venous blood, mononuclear cells were isolated and stored in the freezer. Using multicolor flow cytometry T-, NK cell and monocyte subpopulations were determined. After characterization of the immune cell subsets, TIGIT, CD226, CD112, and CD155 surface expression and intracellular granzyme B content were determined by flow cytometer. Significantly decreased CD226 expression and increased CD112 and CD155 surface expression were detected in almost all investigated T-cell, NK cell, and monocyte subpopulations in women diagnosed with preeclampsia compared to the healthy group. Furthermore, reduced TIGIT and granzyme B expression were measured only in preeclamptic CD8+ T cells compared to healthy pregnant women. A decreased level of the activatory receptor CD226 in effector lymphocytes accompanied with an elevated surface presence of the CD112 and CD155 ligands in monocytes could promote the TIGIT/CD112 and/or TIGIT/CD155 ligation, which mediates inhibitory signals. We assume that the inhibition of the immune response via this immune checkpoint pathway might contribute to compensate for the Th1 predominance during early-onset preeclampsia.

We investigated peripartum maternal red blood cell (RBC) properties in early-onset preeclampsia (PE). Repeated blood samples were taken prospectively for hemorheological measurements at PE diagnosis (n = 13) or during 26–34 weeks of gestation in healthy pregnancies (n = 24), then at delivery, and 72 h postpartum. RBC aggregation was characterized by M index (infrared light transmission between the aggregated RBCs in stasis) and aggregation index (AI—laser backscattering from the RBC aggregates). We observed significantly elevated RBC aggregation (M index = 9.8 vs. 8.5; AI = 72.9% vs. 67.5%; p < 0.001) and reduced RBC deformability in PE (p < 0.05). A positive linear relationship was observed between AI and gestational age at birth in PE by regression analysis (R² = 0.554; p = 0.006). ROC analysis of AI showed an AUC of 0.84 (0.68–0.99) (p = 0.001) for PE and indicated a cutoff of 69.4% (sensitivity = 83.3%; specificity = 62.5%), while M values showed an AUC of 0.75 (0.58–0.92) (p = 0.019) and indicated a cutoff of 8.39 (sensitivity = 90.9% and specificity = 50%). The predicted probabilities from the combination of AI and M variables showed increased AUC = 0.90 (0.79–1.00) (p < 0.001). Our results established impaired microcirculation in early-onset PE manifesting as deteriorated maternal RBC properties. The longer the pathologic pregnancy persists, the more pronounced the maternal erythrocyte aggregation. AI and M index could help in the prognostication of early-onset PE, but further investigations are warranted to confirm the prognostic role before the onset of symptoms.

Preeclampsia is the leading cause of complicated neonatal adaptation. The present investigation aimed to study the hemorheological factors during the early perinatal period (cord blood, 24 and 72 h after delivery) in newborns of early-onset preeclamptic mothers (n = 13) and healthy neonates (n = 17). Hematocrit, plasma, and whole blood viscosity (WBV), red blood cell (RBC) aggregation, and deformability were investigated. There were no significant differences in hematocrit. WBV was significantly lower in preterm neonates at birth than in the term 24 and 72 h samples. Plasma viscosity was significantly lower in preterm neonates’ cord blood than in healthy controls. RBC aggregation parameters were significantly lower in preterm newborns’ cord blood than in term neonates’ cord blood 24 and 72 h samples. RBC elongation indices were significantly lower in the term group than in preterm neonates 72 h’ sample at the high and middle shear stress range. Changes in the hemorheological parameters, especially RBC aggregation properties, refer to better microcirculation of preterm neonates at birth, which could be an adaptation mechanism to the impaired uteroplacental microcirculation in preeclampsia.

Background: Venous thromboembolism is more prevalent among patients with inflammatory bowel disease (IBD). This study aimed to identify prothrombotic hemorheological alterations in IBD. Methods: We conducted a case–control study with patients with ulcerative colitis, Crohn’s disease, and non-IBD control subjects. We measured hemorheological indicators including plasma viscosity (PV), whole blood viscosity (WBV), erythrocyte aggregation (EA), and erythrocyte deformability (ED). Uni- and multivariate tests were employed for analysis. Results: A total of 53 IBD patients and 77 control subjects were recruited. IBD patients showed significantly higher aggregation index (68.8% (35.3–83.5%) vs. 66.9% (35.2–83.5%), p = 0.003) and threshold shear rate (120 1/s (55–325 1/s) vs. 110 1/s (55–325 1/s), p < 0.001), with lower aggregation half-time (1.6 s (0.6–7.1 s) vs. 1.8 s (0.6–7.1 s), p = 0.004), indicating enhanced EA. However, after adjusting for covariates, including inflammatory markers, IBD no longer predicted EA. There were no significant differences in EA. PV, WBV, and ED between the groups. Fibrinogen, rather than the Crohn’s Disease Activity Index, was the strongest predictor of the outcomes. Conclusions: Our study demonstrates that IBD patients exhibit enhanced EA, predicted mainly by fibrinogen. These results confirm that inflammation plays the cardinal role in the increased tendency for venous thromboembolism in IBD.