Role of immunity indices of pregnant women for prognosis of fetoplacental insufficiency development
Last reviewed: 23.04.2024
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A study was conducted to determine cytokines in patients in the second trimester of pregnancy. It was found that the immune disorders in the presence of signs of chronic fetoplacental insufficiency (FPN) are manifested by an increase in TNF-a production and a simultaneous decrease in IL-4, IL-10, IL-13 cytokines, which proves their role in predicting the probable risk of FPN development.
Despite intensive studies of the pathogenesis of fetoplacental insufficiency (FPN), immune abnormalities in this pathology remain insufficiently studied. In particular, there is no information in the literature on any diagnostically important immunological markers that could serve as predictors of the development of fetoplacental insufficiency. Of particular interest in this aspect are studies of the balance of proinflammatory and anti-inflammatory cytokines. As is known, with physiological pregnancy, the balance shifts toward the dominance of immunosuppressive cytokines, which promote the development of immunological tolerance to fetal alloantigens.
The purpose of this study was a retrospective evaluation of immunity indices in the second trimester of pregnancy in women with the absence and development of FPN.
Analysis of immunological parameters in the II trimester (in terms of 16 to 22 weeks) was carried out in 32 pregnant women, which were divided into 2 groups: 1 st - with complicated course of pregnancy and presence of signs of chronic FPN (n = 19) and 2nd - with physiological pregnancy, absence of signs of chronic FPN (n = 13). Groups of pregnant women were comparable in age (30.2 ± 0.8 and 32.3 ± 0.6 years) and gestational age (18.8 ± 0.7 and 18.3 ± 0.5 weeks).
In the 1st group, the course of pregnancy was complicated by the threat of termination of pregnancy (8 cases), immunological conflict (6), anemia of pregnant women (5), intrauterine infection (4), kidney disease (3), and cardiovascular pathology (2 cases).
Spontaneous production of cytokines (TNF-a, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13) was studied in cultures of whole blood cells. Mathematical processing of the obtained results was carried out using the Statistica 6.0 software package.
The analysis of spontaneous production of inflammatory (TNF-a, IL-2JL-12,) and anti-inflammatory (IL-4, IL-5, IL-10, IL-13) cytokines by whole blood cells of women examined in the second trimester of pregnancy revealed a significant increase the average level of production of TNF-a in pregnant women of the 1st group. In 10 (52.6%) of 19 women in this group, spontaneous production of TNF-a exceeded the upper limit of the range, characteristic for women with a physiological pregnancy. It should be noted that in both groups there was a significant variability in the production of cytokines at the level of individual values. Nevertheless, a comparative analysis of the indices revealed a distinct tendency in pregnant women with fetoplacental insufficiency to reduce the intensity of production of such cytokines as IL-4 (48.7 ± 19.6), IL-10 (0.4 ± 0.6) and IL- 13 (43.1 + 11.6) compared with the physiological course of pregnancy (116.3 ± 43.6, 2.6 ± 1.2 and 106.7 ± 75.3, respectively). In 36.8-57.9% of women in group 1, the level of production of these cytokines exceeded the lower limit of the range of median acceptable values (median).
The shift in the cytokine balance towards proinflammatory cytokines due to an increase in TNF-a and a simultaneous decrease in IL-4, IL-10, IL-13 was clearly manifested by an increase in the indices of the ratio of TNF-a / Th-4, TNF-a / IL-101 and TNF- a / 1b-13 (p <0,05) in groups of women with physiological pregnancy and fetoplacental insufficiency, respectively. In this case, the frequency of occurrence of pregnant women with fetoplacental insufficiency, in which in II trimester the values of these indices exceeded the upper limit of the range of healthy pregnant women, were 63 and 57.9%, respectively.
Violation of the cytokine balance is apparently not accidental, since it is confirmed by an evaluation of the biological activity of serum factors. Thus, in comparison with healthy pregnant women in females with fetoplacental insufficiency, a statistically significant decrease in the suppressor activity of serum was detected. At the same time, the index of suppressor activity (ISA) was in women with physiological pregnancy - 0.59 ± 0.06 calc. Units (p <0.05). These data show that in pregnant women with fetoplacental insufficiency, imbalance of cytokines and a decrease in the activity of anti-inflammatory cytokines (IL-10, IL-13, IL-4) are observed.
Proinflammatory cytokines (IL-2JL-12) in the 1 st group of patients with complicated pregnancy progress changed insignificantly and were unreliable (p> 0.05).
The data obtained by us indicate that individual immunological indices can serve as prognostic factors in the development of fetoplacental insufficiency. Thus, it has been established that in pregnant women with fetoplacental insufficiency developed in the second trimester, cytokine balance is violated towards the dominance of proinflammatory cytokines due to an increase in TNF-α production and a simultaneous decrease in IL-10 and IL-13, which is manifested by an increase in indices of the ratio of TNF- a / IL-101 and TNF-a / IL-13, as well as a decrease in the suppressor activity of serum factors.
It is believed that a certain level of TNF-a is necessary for the normal development of pregnancy, as it limits the processes of DNA synthesis by trophoblast cells that express receptors for TNF-a. However, excessive production of TNF-a leads to a disruption of microcirculation and tissue hypoxia, which can adversely affect the development of pregnancy. As a result, there is a progressive decrease in uteroplacental blood flow and a violation of the metabolic, trophic, and hormonal functions of the placenta. In the serum of pregnant women with fetal growth retardation syndrome, elevated concentrations of TNF-a are noted. Our results suggest that increased spontaneous production of TNF-a (> 30 pg / ml) and a simultaneous decrease in IL-4, IL-10 and IL-13 can act as a highly specific (91%) predictor of the likely risk of fetoplacental insufficiency .
On the basis of the study, it can be concluded that the formation of fetoplacental insufficiency is associated with immune dysfunctions arising in the second trimester of pregnancy. Immune disorders are manifested by increased production of TNF-a and a simultaneous decrease in IL-4, IL-10, IL-13. The assessment of the specificity and sensitivity of these immunological parameters has shown the potential for their use as additional predictor factors in the development of a diagnostic model that is effective in predicting the likely risk of fetoplacental insufficiency.
Prof. I.Yu. Kuz'mina. The role of immunity indices of pregnant women for prognosis of fetoplacental insufficiency development // International Medical Journal - №3 - 2012
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