Features of the Immune System Functioning with Persistence of Infectious Agents in Women with Chronic Endometrial Inflammation and Reproductive Disorders

Abstract

The objective of our study was to investigate the specific features of immune status indicators in women of reproductive age with chronic endometritis (CE) and reproductive disorders. Methods and Results: The observational study involved 81 women of reproductive age with reproductive disorders. The main group (MG) included 50 women with CE (mean age of 29.2±5.34 years). The control group (CG) consisted of 31 fertile women also of reproductive age(mean age of 30.7 ± 5.9 years). MG was divided into the following subgroups: Subgroup A (SubA) included 31 patients with verified CE and an isolated infectious agent from endometrial tissue: Subgroup B (SubB) included 19 patients with verified CE and the absence of an infectious agent in the endometrial tissue. Endometrial aspiration pipe biopsy was performed on days 4-9 of the menstrual cycle (middle proliferative phase) using a disposable intrauterine probe (Taizhou Kechuang Medical Apparatus Co., Ltd, China) followed by histological examination of endometrial tissue. Laboratory diagnostics for sexually transmitted infections (STIs) was performed using the bacterial culture method. For the diagnosis of viral infection (HPV, HSV, CMV), cervical samples were studied using PCR. If STIs were detected, the patients were excluded from further research. Ultrasound examination of the pelvic organs was performed using the Aloka-5500 device with a 7MHz vaginal probe in two-dimensional visualization mode. The concentration of cytokines (IL-1β, INF-γ, TNF-α, ILs-4,6,8,10) in the endometrium was determined using the Protein Contour test systems (Saint Petersburg) and Multiskan EX ELISA Analyzer (Germany). The percentages and absolute counts of blood lymphocytes (CD3+, CD3+/CD8+/CD45+, CD19+/CD45+, and CD16+/CD56+/CD45+ cells) were determined by the method of indirect immunofluorescence with monoclonal antibodies using the BD FACSCalibur flow cytometer (USA). We found a significant increase in the blood concentrations of CD3+ cells, CD3+/CD8+/CD45+ cells, and CD19+/CD45+ cells and a decrease in the levels of CD16+/CD56+/CD45+ cells, microbicidal activity of oxygen-dependent function of neutrophils, and phagocytic activity of neutrophils, as well as a significant decrease in the levels of IgA, IgM, and IRI in MG, compared to CG. In SubA, compared to SubB, we found a significant decrease in CD3+ cells and CD19+/C45+ cells and a slight increase in immunoregulatory index. The concentrations of tissue cytokines in women of MG were characterized by a 3-fold increase in the level of pro- and anti-inflammatory cytokines (IL-1β, ILs - 4, 6, 10, and INF-γ), and a 4-fold increase in the levels of TNF-α and IL-8, compared to CG. In SubA, in comparison with SubB, a significant decrease in anti-inflammatory cytokines (ILs-4,10) and chemokine IL-8 was revealed against the background of a significant increase in the concentrations of INF–γ and TNF–α. Conclusion: The results obtained indicate changes in the reactivity of the immune system in women with reproductive disorders and chronic inflammation in the endometrium. The most pronounced changes in the local immunity indicators are observed when opportunistic pathogens are detected in the endometrial tissue.