POSSIBILITIES OF CORRECTING CELLULAR-HUMORAL IMMUNE DISORDERS AND CYTOKINE STATUS IN HIGH-RISK PREGNANT WOMEN FOR THE DEVELOPMENT OF PREECLAMPSIA

Abstract

The development of pre-eclampsia is associated with immunological interactions between the foreign maternal and fetaltissues, which are characterized by a predominance of the infl uence of type 1 T-helper cells, leading to increased production of highly aggressive pro-infl ammatory cytokines. However, the mechanism of cellular- humoral immune and cytokine changes leading to the manifestation of pre-eclampsia is not fully understood and no corrective measures have been developed.Purpose. To investigate the changes in the cellular- humoral immunity and cytokine profi le in a cervical mucus of pregnantwomen at high risk for developing PE and to fi nd out the eff ectiveness of the proposed secondary prevention of PE in thenormalization of these indicators.Method and Materials. The main group (MG) consisted of 91 pregnant women with risk factors for pre-eclampsia whohad impaired blood fl ow in the uterine spiral arteries at 18-20 weeks of pregnancy. Among them, 59 patients (MG-II) received secondary prevention of pre-eclampsia from 18-20 weeks until delivery using metformin, vitamin D3, and corvitin, while the remaining 32 patients (MG-I) declined preventive measures. The control group (CG) consisted of 30 healthy pregnant women. The research was regulated by the rules of humane treatment of patients in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the international recommendations of the Helsinki Declaration on Human Rights, the Convention of the Council of Europe on Human Rights and Biomedicine, and the laws of Ukraine. TNF-α, INFγ and IL-10 levels were determined in cervical mucus by enzyme- linked immunosorbent assay (ELISA); peripheral blood lymphocyte CD3+, CD4+, CD8+, CD16+, CD22+ levels were assessed by indirect immunofl uorescence. The CD4/CD8 ratio was calculated as an immunoregulatory index. Blood serum immunoglobulin (Ig) levels were determined by competitive enzyme- linked immunosorbent assay (A, M, and G). The concentration of circulating immune complexes (CIC) in blood serum was measured by the immunoturbidimetric assay. The data were analyzed by mathematical- statistical methods, calculating the mean (M), variance (σ), and standard error (m), applying Student’s t-test, and performing correlation analysis using the statistical program «STATISTICA» (StatSoft Inc., USA). The paper is an excerpt from the initiative scientifi c research project of the Department of Obstetrics and Gynecology № 2 of the Poltava State Medical University entitled «Optimization of approaches to management of pregnancy in women at high risk of obstetric and perinatal pathology» (state registration number 0122U201228, duration: 10.2022-09.2027).Results. In women at high risk of developing pre-eclampsia (MG-I), a signifi cant decrease in the concentration of T helpercells (CD4+), an increase in T suppressor/killer cells (CD8+), a decrease in the immunoregulatory index, a decrease in B cells(CD22+) and an increase in CIC were observed. In addition, CIC greater than 100 IU/ml strongly correlated with the development of pre-eclampsia. IgM levels were signifi cantly elevated in women with pre-eclampsia, indicating possible trophoblastic stimulation of their immune system, while IgG levels were signifi cantly reduced. Women with pre-eclampsia had a signifi cant predominance of pro-infl ammatory cytokines and a defi ciency of anti-infl ammatory cytokines. In women of the MG-II group who received the proposed complex of secondary prevention of pre-eclampsia, the content of T-helper cells (CD4+) and T-suppressor/killer cells (CD8+) was normalized. The immunoregulatory index increased signifi cantly, and the number of CD22+ cells was about the level observed in healthy pregnant women. The concentrations of IgA and IgG increased to the levels observed in the control group, while the level of IgM decreased. The level of CIC decreased in pregnant women with MG-II, in contrast to the levels observed in women with MG-I. The levels of pro-infl ammatory cytokines INF-γ and TNF-α decreased after preventive treatment. However, the levels of the antiinfl ammatory cytokine IL-10 increased signifi cantly in MG-II, leading to a signifi cant reduction in the TNF-α/IL-10 ratio (p<0.001).Conclusions. Pregnant wo men with a history of increased risk factors for PE and a decrease in the intensity of bloodfl ow in the spiral arteries of the uterus at 18-20 weeks of gestation have a pronounced imbalance of the T-cell subpopulation, which is accompanied by a decrease in the production of T-helpers (CD4+) and an increase in the synthesis of T-suppressors/ killers (CD8+), which causes a decrease in the immunoregulatory index. This is accompanied by the development of a cytokine imbalance  with a predominance of pro-infl ammatory cytokines and a defi ciency of anti-infl ammatory cytokines, and is also associated with a signifi cant decrease in the concentration of IgG and a decrease in the number of B cells. Such changes are a consequence of the exhaustion of the reactivity of the humoral link of the general immunity, creating the conditions for the frequent manifestation of PE, which occurs in almost half of such women. The application of our proposed improved method of secondary prevention of pulmonary embolism in pregnant women with a high risk of developing this disease leads to signifi cant positive changes in the work of the immune system and a corresponding improvement in clinical results. It makes it possible to reduce the frequency of PE development by 1.4 times and to prevent the occurrence of its severe forms by 2.6 times.