Role of immunity indices of pregnant women in predicting the development of fetoplacental insufficiency

A study was conducted to determine cytokines in patients in the second trimester of pregnancy. It was found that immune disorders in the presence of signs of chronic fetoplacental insufficiency (FPI) are manifested by increased production of TNF-a and a simultaneous decrease in cytokines IL-4, IL-10, IL-13, which proves their role in predicting the probable risk of developing FPI.

Despite intensive studies of the pathogenesis of fetoplacental insufficiency (FPI), immune disorders in this pathology remain insufficiently studied. In particular, there is no information in the literature on any diagnostically significant 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, during physiological pregnancy, there is a shift in the balance towards the dominance of immunosuppressive cytokines, which contribute to the development of immunological tolerance to fetal alloantigens.

The aim of this study was to retrospectively evaluate immunity indicators in the second trimester of pregnancy in women with the absence and development of FPN.

The analysis of immunological parameters in the second trimester (from 16 to 22 weeks) was performed in 32 pregnant women, who were divided into 2 groups: the 1st group - with complicated pregnancy and the presence of signs of chronic FPN (n = 19) and the 2nd group - with physiological pregnancy, the absence of signs of chronic FPN (n = 13). The 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 whole blood cell cultures. Mathematical processing of the obtained results was performed using the Statistica 6.0 software package.

Analysis of spontaneous production of proinflammatory (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 reliable increase in the average level of TNF-a production in pregnant women of the 1st group. In 10 (52.6%) of 19 women of this group, spontaneous production of TNF-a exceeded the upper limit of the range typical for women with a physiological course of pregnancy. It should be noted that in both groups, significant variability in cytokine production was revealed at the level of individual values. Nevertheless, a comparative analysis of the indicators revealed a clear tendency for a decrease in 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) in pregnant women with fetoplacental insufficiency compared to 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 the 1st group, the level of production of these cytokines went beyond the lower limit of the range of average acceptable indicators (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 TNF-a/IL-4, TNF-a/IL-10 and TNF-a/IL-13 ratio (p < 0.05) in the groups of women with physiological pregnancy and fetoplacental insufficiency, respectively. At the same time, the frequency of occurrence of pregnant women with fetoplacental insufficiency, in whom the values of these indices in the second trimester were beyond the upper limit of the range of healthy pregnant women, was 63 and 57.9%, respectively.

The cytokine imbalance is apparently not accidental, since it is confirmed by the assessment of the biological activity of serum factors. Thus, compared with healthy pregnant women, statistically significant weakening of the suppressor activity of the blood serum was revealed in women with fetoplacental insufficiency. At the same time, the suppressor activity index (SAI) in women with physiological pregnancy was 0.59±0.06 calculated units (p < 0.05). These data show that pregnant women with fetoplacental insufficiency have an imbalance of cytokines and weakening of the activity of anti-inflammatory cytokines (IL-10, IL-13, IL-4).

Proinflammatory cytokines (IL-2JL-12) in the 1st group of patients with complicated pregnancy changed insignificantly and were insignificant (p>0.05).

The data we obtained indicate that individual immunological indices may act as prognostic factors for the development of fetoplacental insufficiency. Thus, it has been established that in pregnant women with subsequently developed fetoplacental insufficiency, already in the second trimester, a violation of the cytokine balance is observed towards the dominance of proinflammatory cytokines due to an increase in the production of TNF-a and a simultaneous decrease in IL-10 and IL-13, which is manifested by an increase in the indices of the TNF-a/IL-10 and TNF-a/IL-13 ratio, as well as a weakening of the suppressor activity of serum factors.

It is believed that a certain level of TNF-a is necessary for normal pregnancy development, 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 microcirculation disorders and tissue hypoxia, which can negatively affect pregnancy development. As a result, there is a progressive decrease in uteroplacental blood flow and a violation of the metabolic, trophic, hormonal function of the placenta. Increased concentrations of TNF-a are noted in the serum of pregnant women with fetal growth retardation syndrome. Our results indicate that increased spontaneous production of TNF-a (more than 30 pg/ml) and a simultaneous decrease in IL-4, IL-10 and IL-13 can act as a highly specific (91%) prognostic factor for the probable risk of fetoplacental insufficiency.

Based on the conducted study, it can be concluded that the formation of fetoplacental insufficiency is associated with immune dysfunctions that occur 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 conducted assessment of the specificity and sensitivity of these immunological parameters showed the potential for their use as additional predictor factors in creating a diagnostic model effective in predicting the probable risk of developing fetoplacental insufficiency.

Prof. I. Yu. Kuzmina. The role of indicators of immunity of pregnant women for the prognosis of development of fetoplacental insufficiency // International Medical Journal - No. 3 - 2012

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