Верификација на имунолошката компонента во етиопатогенезата на прееклампсијатa

Abstract

Introduction Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide. Preeclampsia is a multi-systemic disorder found in 5-10% of pregnancies. Its etiopathogenesis is multifactorial and is still a challenge and a subject of research. Generalized endothelial dysfunction in the preeclampsia also occurs due to an exacerbation of the systemic inflammatory response described by imbalance of proinflammatory and antiinflammatory cytokines. Aim The aims of the research in the doctoral dissertation are as follows: - Prediction of the occurrence of preeclampsia in patients appearing in the PHI University Clinic of Gynaecology and Obstetrics - Skopje in the second trimester, from 14 to 20 gestational weeks, using previously ultrasound verification of notch of the uterinee artery; - Determination of possible risk of developing preeclampsia by examining the following biochemical parameters: TNF-α, IL-1α, IL-2, IL-6 versus IL-4 and IL-10, as confirmation of the immunological origin of preeclampsia; -Analyzing the rate of increase or decrease in the value of cytokines in addition to preeclampsia and -Monitoring patients until and after giving birth, with aim to present pregnant women who have actually developed preeclampsia syndrome, diagnosed clinically and by laboratory tests, as well as the outcome of those pregnancies, the way the pregnancies are completed, at which gestation week, and the weight of the newborn with AC. Materials and methods There were 100 patients, 50 of which comprised the study group with a notch on the uterine artery investigating the production discrepancies and the relationship between proinflammatory and anti-inflammatory cytokines (TNF-α, IL-1α, IL-2, IL-6, vs. IL-4, IL-10) by ELISA (enzyme-linked immunosorbent assay) methodology. In addition to this group, a control group of 50 patients with absent uterine artery notch was examined to compare and draw appropriate conclusions. Parameters that were used, in addition to the notch, were the Resistance Index (RI) and the Pulsatile Index (PI), both more specific and sensitive. The results were subjected to statistical analysis and processing with computer programs: STATISTICA 12 and SPSS 21.0 for Windows. On this basis, tests for the significance of differences between the comparison groups of all analyzed parameters were performed. The Ethics Committee of the Faculty of Medicine in Skopje agrees with the research. Results The results of increased proinflammatory and decreased regulatory anti-inflammatory immune cells and cytokines explain the uncontrolled state of inflammation. In the patients with established uterine notch, pulsatile RI and PI values above 0.68 and 1.75 are abnormal and correlate with increased proinflammatory interleukins (with cut-off values for RI 0.72 and PI with a cut-off of 2.01) which is an important predictive indicator of statistical significance. The probability that the patient has a risk of developing a pathological condition such as preeclampsia is confirmed by her serum laboratory findings through an increase in proinflammatory biomarkers (IL-6, TNF-α, along with IL-6 and TNF-α in correlation with IL-1α with p <0.01) and a decrease in anti-inflammatory (IL-10) biomarker, prior to the development of the patient's clinical condition, and is a signal for preventive action. This disorder is thought to contribute to the overall pathophysiology of preeclampsia. Patients who developed clinical preeclampsia syndrome had statistically significant changes p<0.05 in laboratory parameters in addition to multi-organ damage. Significant differences were found for systolic and diastolic blood pressure at p<0.01, compared with a control group of relatively healthy patients. Significant differences were also found with p<0.05 in relation to ALT, LDH, CRP, total proteins, urea, uric acid, creatinine kinase, GGT, proteinuria and 24 hour proteinuria, haemoglobin and haemostasis and D-dimer results. There is a positive correlation between the interleukin IL-6 values and LDH, CRP and total protein parameters with significant level of significance p<0.01 in addition to preeclampsia as an important parameter and criteria for its prediction. 10 There was a significant difference in gestational week in favour of more frequent preterm birth in preeclampsia patients, but no statistically significant results were obtained in terms of body weight and Apgar scores of new borns. It is of particular importance for the assessment of overall maternal and fetal morbidity and mortality. Conclusion Immune biomarkers compared in both groups differ and may be taken as prognostic criteria in the subsequent early detection of clinical preeclampsia syndrome. Uterine artery Doppler results and interleukin-altered values have a predictive value and give this test a significantly higher sensitivity and specificity. The importance of prediction is perceived in order to enable the prevention of the pathological condition by appropriate treatment, counselling, hygienic diet and careful monitoring of the health of both the mother and the fetus. Therefore, it is suggested to implement the Doppler Uterine Artery as a routine examination, and if abnormal result is present, to determine the immunological biomarkers. It is aimed at timely prediction, prevention, diagnosis and treatment of the preeclampsia which is vital for the preservation of the life and health of the mother, and therefore of the fetus.