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Background: Immunological imbalances characteristic of endometriosis may develop as early as the primary manifestations of the disease in adolescence. Objective: To evaluate subpopulation dynamics of monocytes and lymphocytes in peripheral blood and peritoneal fluid of adolescents with peritoneal endometriosis at diagnosis and after 1-year progestogen therapy. Methods: This study included 70 girls, 13–17 years old, diagnosed laparoscopically with peritoneal endometriosis (n = 50, main group) or paramesonephric cysts (n = 20, comparison group). Phenotypes of monocytes and lymphocytes of the blood and macrophages of the peritoneal fluid were analyzed by flow cytometry at diagnosis and during progestogen therapy. Results: Differential blood counts of CD16+ (p < 0.001) and CD86+ (p = 0.017) monocytes were identified as independent risk factors for peritoneal endometriosis in adolescents. During the treatment, cytotoxic lymphocytes CD56dimCD16bright (p = 0.049) and CD206+ monocytes (p < 0.001) significantly increased while CD163+ monocytes decreased in number (p = 0.017). The CD56dimCD16bright blood counts before (p < 0.001) and during progestogen therapy (p = 0.006), as well as CD206+ blood counts during the treatment (p = 0.038), were associated with the efficacy of pain relief after 1-year progestogen therapy. Conclusions: Adolescents with peritoneal endometriosis have altered counts of pro- and anti-inflammatory monocytes and lymphocytes both before and after 1-year progestogen therapy, correlating with treatment efficacy and justifying long-term hormonal therapy.

Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (12 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection.

Aim. To asses an effectiveness of assisted reproductive technologies (ART) program given characteristics of the cytokine profile of seminal plasma (SP) entering the female reproductive tract during sexual intercourse. Outcomes and methods. 33 married couples who applied for a treatment of infertility by means of in vitro fertilization /ICSI (Intracytoplasmic Sperm Injection) were included in the prospective study. Patients were recommended to have sexual intercourse with no restrictions during treatment and to have the last sexual intercourse 3 days before an intended transvaginal puncture (ITP). Testing of cytokines (transforming growth factor (TGF)-b1, interferon (IFN)-g, interleukin (IL)-33, IL-6, IL-8, IL-23, IL-10, tumor necrosis factor (TNF)-a, IL-18, IL- 17A, IFN-a, IL-12, monocyte chemotactic protein-1) levels in samples of partners’ SP obtained on the day having ITP were carried out using multiplex analysis with LegendPlex kits (BioLegend, USA). Results. When comparing a cytokine profile of SP in couples who did not become pregnant (n=25) and couples who become pregnant (n=8) increased IL-18 and reduced IL-10 levels (p=0,017 and p=0, 01 respectively) were revealed in the group which got pregnant. To assess a clinical relevance of cytokine content in SP ROC (Receiver Operating Characteristics) curve was used. It was established that determining of IL-18 concentration in SP has the greatest diagnostic significance (the area under a curve was 0.792±0.107, test sensitivity - 62.5%, test specificity - 95.24% at threshold concentration>210.43 pg/ml). Incidence of pregnancy at IL-18 concentration above threshold levels was 83,3% while at lower concentrations of IL-18 pregnancy occurred only in 13.0% of women. Conclusions. Elevated IL-18 levels and decreased IL-10 levels in SP of female patients’ partners who don’t have restriction of sexual life when treating infertility with ART are favorable factors for a pregnancy to occur.

One of the causes of death of patients infected by SARS-CoV-2 is the induced respiratory failure caused by excessive activation of the immune system, the so-called “cytokine storm”, leading to damage to lung tissue. In vitro models reproducing various stages of the disease can be used to explore the pathogenetic mechanisms and therapeutic approaches to treating the consequences of a cytokine storm. We have developed an in vitro test system for simulating damage to the pulmonary epithelium as a result of the development of a hyperinflammatory reaction based on the co-cultivation of pulmonary epithelial cells (A549 cells) and human peripheral blood mononuclear cells (PBMC) primed with lipopolysaccharide (LPS). In this model, after 24 h of co-cultivation, a sharp decrease in the rate of proliferation of A549 cells associated with the intrinsic development of oxidative stress and, ultimately, with the induction of PANoptotic death were observed. There was a significant increase in the concentration of 40 cytokines/chemokines in a conditioned medium, including TNF-α, IFN-α, IL-6, and IL-1a, which corresponded to the cytokine profile in patients with severe manifestation of COVID-19. In order to verify the model, the analysis of the anti-inflammatory effects of well-known substances (dexamethasone, LPS from Rhodobacter sphaeroides (LPS-RS), polymyxin B), as well as multipotent mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (EVs) was carried out. Dexamethasone and polymyxin B restored the proliferative activity of A549 cells and reduced the concentration of proinflammatory cytokines. MSC demonstrated an ambivalent effect through stimulated production of both pro-inflammatory cytokines and growth factors that regenerate lung tissue. LPS-RS and EVs showed no significant effect. The developed test system can be used to study molecular and cellular pathological processes and to evaluate the effectiveness of various therapeutic approaches for the correction of hyperinflammatory response in COVID-19 patients.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.

The breastfeeding of infants by mothers who are infected with SARS-CoV-2 has become a dramatic healthcare problem. The WHO recommends that infected women should not abandon breastfeeding; however, there is still the risk of contact transmission. Convalescent donor milk may provide a defense against the aforementioned issue and can eliminate the consequences of artificial feeding. Therefore, it is vital to characterize the epitope-specific immunological landscape of human milk from women who recovered from COVID-19. We carried out a comprehensive ELISA-based analysis of blood serum and human milk from maternity patients who had recovered from COVID-19 at different trimesters of pregnancy. It was found that patients predominantly contained SARS-CoV-2 N-protein-specific immunoglobulins and had manifested the antibodies for all the antigens tested in a protein-specific and time-dependent manner. Women who recovered from COVID-19 at trimester I–II showed a noticeable decrease in the number of milk samples with sIgA specific to the N-protein, linear NTD, and RBD-SD1 epitopes, and showed an increase in samples with RBD conformation-dependent sIgA. S-antigens were found to solely induce a sIgA1 response, whereas N-protein sIgA1 and sIgA2 subclasses were involved in 100% and 33% of cases. Overall, the antibody immunological landscape of convalescent donor milk suggests that it may be a potential defense agent against COVID-19 for infants, conferring them with a passive immunity.