Diagnostic accuracy of the IDEA protocol for non invasive diagnosis of rectosigmoid DE - a prospective cohort study.

OBJECTIVES: To test the accuracy of TVS applying the IDEA approach for suspected rectosigmoid DE and to determine the frequency of other pelvic diseases mimicking DE in patients undergoing surgery. MATERIALS UND METHODS: Prospective single center observational study including consecutive women undergoing TVS for clinically suspected rectosigmoid DE followed by conservative or surgical therapy. TVS findings were compared with those obtained by laparoscopy and confirmed histologically. RESULTS: Of the 671 included patients, 128 women opted for medical therapy, and 6 patients decided for surgery but did not give consent to participate in the study. 537 women were enrolled in the final analysis. 279 (52 %) exhibited surgically confirmed rectosigmoid DE. The sensitivity and specificity, positive and negative predictive value (PPV, NPV), positive and negative likelihood ratio (LR+/-) and accuracy of TVS for diagnosing DE in the rectosigmoid were 93.5 %, 94.6 %, 94.9 %, 93.1 %, 17.24, 0.07, 94.04 %. 12 women who were clinically suspected for DE and mimicked sonographic signs fulfilling the IDEA criteria did exhibit other pathologies. Diagnoses were as follows: vaginal Gartner duct cyst (3/291;1.0 %), anorectal abscess (3/291; 1.0 %), rectal cancer (2/291;0.7 %), hydrosalpinx (2/291;0.7 %), metastatic endometrial cancer (1/291;0.35 %) and Crohn's disease (1/291;0.35 %). CONCLUSION: TVS for diagnosing colorectal DE applying the IDEA criteria is highly accurate for presurgical diagnosis. However, additional pelvic pathologies are encountered in 4-5 % of women attending for suspected rectosigmoid DE. These need to be taken into account when investigating patients for suspected DE.

Upregulation of exofacial peroxiredoxin-thioredoxin system of lymphocytes and monocytes in preeclampsia.

OBJECTIVES: An imbalanced redox homeostasis resulting in oxidative stress is present in preeclampsia. Peroxiredoxin-1 (PRDX1) and thioredoxin-1 (TRX1) regulatory enzymes are also contributing to the redox homeostasis, but were not investigated so far in preeclampsia. Thus, we have aimed to characterize PRDX1, TRX1 and oxidative stress biomarkers in blood samples of pregnant women with preeclampsia. STUDY DESIGN: Twelve patients with preeclampsia (PE) were enrolled into the study. Seven third trimester healthy pregnant women (HP) were accepted as control group. MAIN OUTCOME MEASURES: Peripheral venous blood samples of healthy and preeclamptic pregnant women were analyzed. Plasma level of advanced oxidation protein products (AOPP) was determined by spectrophotometry. The exofacial PRDX1 and TRX1 expression of lymphocytes and monocytes was detected by flow cytometry. RESULTS: The plasma AOPP level was significantly higher in preeclampsia compared to the healthy pregnant group. Significantly higher percentage of PRDX1 and TRX1 expressing lymphocytes and monocytes were detected in the blood samples of preeclamptic women compared to healthy pregnant controls. The ratio of circulating PRDX1 and TRX1 expressing lymphocytes and monocytes showed a significant inverse correlation with the birth weight of newborns. CONCLUSIONS: We have revealed that the level of advanced oxidation protein products is increased and the exofacial peroxiredoxin-1 and thioredoxin-1 system in lymphocytes and monocytes is upregulated in preeclampsia. In addition, the ratio of peroxiredoxin-1 and thioredoxin-1 positive circulating lymphocytes and monocytes correlates inversely with the neonatal birth weight, which finding indicates that pregnancies complicated by intrauterine growth restriction are accompanied by a higher level of oxidative stress.

The applicability of the Eating Disorder Inventory in pregnancy.

PURPOSE: The aim of our study was validating Eating Disorder Inventory (EDI) among pregnant women, who are vulnerable to eating disorders (EDs). METHODS: In 2012-2013, 1146 women (aged 18-47 years) completed a questionnaire including EDI during the first 3 days after delivery. We checked factorial validity of three diagnostic subscales of EDI with confirmative factor analysis and internal validity by Cronbach's alpha and item-total correlation. We also tested discriminative validity by comparing average of the three subscale of EDI in case of ED and non-ED groups. RESULTS: When applying the EDI to pregnant women, it seems necessary to exclude five items on three diagnostic subscales: on the Drive for Thinness subscale, 4 items remain (out of 7); on the Bulimia subscale, 6 items remain (out of 7); the Body Dissatisfaction subscale decreases from 9 to 8 items. Cronbach's alpha and item-total correlation values meet the requirements defined by Garner et al. The internal consistency of the EDI has proved to be appropriate, indicating that it is a reliable screening tool. CONCLUSIONS: Thinking, attitudes, and behaviors connected to eating, along with the relation to altering body weight change during pregnancy. Vomiting usually accompanies pregnancy; body weight gain within wide limits is also regarded as normal during pregnancy. These behaviors and changes are not feasible to use for measuring ED symptoms. These aspects cannot be neglected when screening eating disorders in pregnant women. LEVEL OF EVIDENCE: Level IV evidence obtained from multiple time series with or without an intervention.

Platelet-derived extracellular vesicles may contribute to the hypercoagulable state in preeclampsia.

It has previously been shown that preeclampsia is associated with disturbed hemostasis and that extracellular vesicles (EVs) play important role in the regulation of hemostatic homeostasis. Thus, we hypothesized that the altered procoagulant characteristics of circulating platelet-derived EVs may contribute to the disturbed hemostasis in preeclampsia. Using multicolor flow cytometry, we have analyzed both tissue factor expressing procoagulant EVs and platelet-derived EV subpopulations derived from resting and activated thrombocytes by examining them in plasma samples of preeclamptic patients and pregnancy-matched healthy individuals. Compared to pregnancy-matched healthy individuals in preeclamptic patients a significantly (p < 0.05) higher ratio of Annexin-V positive activated platelets and a higher number of CD142+ tissue factor bearing procoagulant EVs were found, whereas the absolute amount of circulating CD41a+ platelet-derived EVs and CD62P+/CD41a+ EVs produced by activated thrombocytes was significantly lower in the plasma of preeclamptic women. In the plasma samples, there was no significant difference in the amount of CD63+ platelet-derived EVs. We propose that increased platelet activation and tissue factor expression of platelet derived extracellular vesicles may contribute to the hypercoagulable state observed in preeclampsia.

Transvaginal Strain Elastosonography May Help in the Differential Diagnosis of Endometriosis?

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Gamma-Synuclein Levels Are Elevated in Peritoneal Fluid of Patients with Endometriosis.

BACKGROUND The role of gamma-synuclein (SNCG) has been widely examined in malignant conditions due to its possible role in disease progression, but very little information is available on its theoretical function on endometriosis formation. MATERIAL AND METHODS Between January 2016 and December 2016, we collected peritoneal fluid and plasma samples from 45 consecutive female patients, of which 15 were without endometriosis, 15 had minimal to mild endometriosis, and 15 had moderate to severe endometriosis. The statistical power was 0.98. We evaluated SNCG levels in the peritoneal fluid and plasma of patients diagnosed with endometriosis, and we compared them with the levels obtained from disease-free control subjects by using enzyme-linked immunosorbent assay. RESULTS SNCG levels were statistically significantly (1.2-fold) higher in the peritoneal fluid of patients with endometriosis compared to controls (p=0.04). We did not find a significant difference between SNCG levels in the plasma of our endometriosis patients and the control group (p=0.086). However, despite previous data showing very limited expression of SNCG in healthy tissues, we found SNCG in the peritoneal fluid of all of the patients in our healthy control group. CONCLUSIONS Levels of SNCG were statistically significantly higher in the peritoneal fluid of patients with endometriosis compared to disease-free controls, which may indicate its possible role the formation and progression of the disease. Moreover, its biological function should be further investigated due to the conflicting results concerning its expression in healthy tissues.

Noninvasive prenatal testing for congenital heart disease - cell-free nucleic acid and protein biomarkers in maternal blood.

Context: Congenital heart disease (CHD) is the most common fetal malformation. Prenatal ultrasonography is routinely applied for the screening of CHD but many factors influence its diagnostic accuracy. The introduction of new biomarkers could facilitate the identification of high-risk pregnancies.Objective: In our review, our aim was to collect expression studies of cell-free nucleic acids and proteins in maternal circulation. Syndromic CHDs which can be detected by noninvasive prenatal testing (NIPT) techniques were also discussed.Methods: PubMed and Web of Science databases were screened for studies where the levels of potential CHD biomarkers were measured in maternal blood samples. Available NIPT tests were collected from the providers' resources.Results: There are nine CHD-associated chromosomal abnormalities, five aneuploidies, and four microdeletions, which are included in NIPT panels. We found eight articles from which five included the analysis of specific cell-free RNA expression and three measurements of protein levels.Conclusions: Most of the common heart-related chromosomal aberrations can be diagnosed by NIPT. Specific cell-free RNAs and circulating proteins seem to be potential biomarkers for fetal CHDs. The application of these new biomarkers could improve the detection rate at early pregnancy, making it possible to provide optimal perinatal and perioperative management.

[Ultrasound diagnosis of fetal adrenal hemorrhage]. / Méhen belül felszívódó magzati mellékvesevérzés ultrahang-diagnózisa.

The confirmed incidence of new-onset adrenal gland hemorrhage has increased with the development of ultrasound diagnostics in recent years. Intrauterine developed cases are rarely recognized. Differential diagnosis of cystic lesions of the adrenal gland is often only possible after birth. In our case study, we report the ultrasonographic diagnosis and follow-up of a cystic lesion measuring 4 × 3 cm in the left fetal epigastrium in the 33rd gestational week. During pregnancy, multimodal imaging methods (both ultrasound and magnetic resonance) have confirmed the diagnosis of hemorrhage in the left adrenal gland. In the 37th gestational week, the hematoma completely resolved. At term, a 4150 gram neonate was delivered in good condition by an elective cesarean section. Postnatal endocrinological and follow-up ultrasound examinations did not find any disorder. This study is the first published case report in the literature that proves that fetal adrenal hemorrhage can intrauterin spontaneously absorb within a short period of time. Our case draws attention to the fact that adrenal bleeding may occur in the newborn regardless of birth trauma. It can also be assumed that the incidence of adrenal bleeding during pregnancy is higher than that reported in neonatal cases. Orv Hetil. 2019; 160(52): 2073-2078.

MASP-1 Increases Endothelial Permeability.

Pathologically increased vascular permeability is an important dysfunction in the pathomechanism of life-threatening conditions, such as sepsis, ischemia/reperfusion, or hereditary angioedema (HAE), diseases accompanied by uncontrolled activation of the complement system. HAE for example is caused by the deficiency of C1-inhibitor (the main regulator of early complement activation), which leads to edematous attacks threatening with circulatory collapse. We have previously reported that endothelial cells become activated during HAE attacks. A natural target of C1-inhibitor is mannan-binding lectin-associated serine protease-1 (MASP-1), a multifunctional serine protease, which plays a key role in the activation of complement lectin pathway. We have previously shown that MASP-1 induces the pro-inflammatory activation of endothelial cells and in this study we investigated whether MASP-1 can directly affect endothelial permeability. All experiments were performed on human umbilical vein endothelial cells (HUVECs). Real-time micro electric sensing revealed that MASP-1 decreases the impedance of HUVEC monolayers and in a recently developed permeability test (XperT), MASP-1 dose-dependently increased endothelial paracellular transport. We show that protease activated receptor-1 mediated intracellular Ca2+-mobilization, Rho-kinase activation dependent myosin light chain (MLC) phosphorylation, cytoskeletal actin rearrangement, and disruption of interendothelial junctions are underlying this phenomenon. Furthermore, in a whole-transcriptome microarray analysis MASP-1 significantly changed the expression of 25 permeability-related genes in HUVECs-for example it up-regulated bradykinin B2 receptor expression. According to our results, MASP-1 has potent permeability increasing effects. During infections or injuries MASP-1 may help eliminate the microbes and/or tissue debris by enhancing the extravasation of soluble and cellular components of the immune system, however, it may also play a role in the pathomechanism of diseases, where edema formation and complement lectin pathway activation are simultaneously present. Our findings also raise the possibility that MASP-1 may be a promising target of anti-edema drug development.

Circulating exosomal and Argonaute-bound microRNAs in preeclampsia.

INTRODUCTION: microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease. OBJECTIVE: Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition. METHODS: PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs. RESULTS: The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed. CONCLUSION: Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.

The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus.

The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ² test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m². The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m² was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele-in interaction with pre-pregnancy BMI-is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.

[Pathophysiology and current clinical approach of ovarian hyperstimulation syndrome]. / Az ovarialis hiperstimulációs szindróma kórélettana és korszeru klinikuma.

During assisted reproduction technologies, controlled hyperstimulation of the ovaries occurs. Ovarian hyperstimulation syndrome is an excessive overreaction of the ovaries complicating pharmacological ovulation induction. Rarely other causes, such as the mutation of the follicle-stimulating hormone receptor may also be in the background. Ovarian hyperstimulation syndrome is clinically characterized by a massive ovarian enlargement associated with an acute third-space fluid shift responsible for the development of ascites, and sometimes pleural or pericardial effusion. Associated arterial or venous thromboembolic symptoms are also common. Ovarian hyperstimulation syndrome is an iatrogenic and potentially life-threatening condition in the form of ischemic stroke or circulatory insufficiency of the limbs. Recently some new methods have been developed for the prevention of the disease. The syndrome affects young, healthy patients. It also has an important economic burden due to the absence from work, bed rest, or hospitalization and intensive medical management of more severe cases. Supportive therapy, anticoagulant prophylaxis and close monitoring are the main approach for the syndrome. However, hospitalization or intervention should not be delayed for patients with severe or critical conditions. Orv Hetil. 2018; 159(34): 1390-1398.

Author Correction: The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effect of maternal depression and anxiety on mother's perception of child and the protective role of social support.

OBJECTIVE: The purpose of this study was to investigate the impact of postpartum depressive and anxiety symptoms on maternal perception of the infant and the protective role of social support. BACKGROUND: Adverse effects of perinatal depression on mother-child interaction are well documented; however, the role of maternal perception has not been examined. METHODS: We used the data of 431 women enrolled in a prospective study in a single maternity unit. Depressive and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS), the State Trait Anxiety Inventory (STAI), and the mother's perception of infant with the Mother's Object Relation Scale (MORS). We used Multidimensional Scale of Perceived Social Support (MSPSS) in order to measure social support. RESULTS: Depressive and anxiety symptoms were positively associated to less positive emotions and a more dominant attitude of child as perceived by mothers. This association was even more significant in the case of trait anxiety. Perceived social support has been found to be a protective factor which was able to reduce this tendency. CONCLUSION: The findings have potential implications for our understanding of the impact of maternal depressive and anxiety symptoms on the developing mother-infant relationship.

Study of patterns of inheritance of premature ovarian failure syndrome carrying maternal and paternal premutations.

BACKGROUND: Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called trinucleotide expansion diseases. Our aim was to analyse the relationship between the paternally inherited premutation (PIP) and the maternally inherited premutation (MIP) by the examination of the family members of women with POF, carrying the premutation allele confirmed by molecular genetic testing. METHODS: Molecular genetic testing was performed in the patients of the 1st Department of Obstetrics and Gynecology with suspected premature ovarian failure. First we performed the southern blot analyses and for the certified premutation cases we used the Repeat Primed PCR. RESULTS: Due to POF/POI, a total of 125 patients underwent genetic testing. The FMR1 gene trinucleotide repeat number was examined in the DNA samples of the patients, and in 15 cases (12%) deviations (CGG repeat number corresponding to premutation or gray zone) were detected. In 6 cases out of the 15 cases the CGG repeat number fell within the range of the so-called gray zone (41-54 CGG repeat) (4.8%, 6/125), and the FMR1 premutation (55-200 CGG repeat) ratio was 7.2% (9/125). In 4 out of the 15 cases we found differences in both alleles, one was a premutation allele, and the other allele showed a repeat number belonging to the gray zone. Out of 15 cases, only maternal inheritance (MIP) was detected in 2 cases, in one case the premutation allele (91 CGG repeat number), while in the other case an allele belonging to the gray zone (41 CGG repeat number) were inherited from their mothers. In 10 out of 15 cases, the patient inherited the premutation allele only from the father (PIP). In 5 out of the 10 cases (50%) the premutation allele was inherited from the father, and the repeat number ranged from 55 to 133. Out of 125 cases, 9 patients had detectable cytogenetic abnormalities (7.2%). CONCLUSIONS: The RP-PCR method can be used to define the smaller premutations and the exact CGG number. Due to the quantitative nature of the RP-PCR, it is possible to detect the mosaicism as well.

Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight: Observations from Our Neonatal Intensive Care Unit (NICU).

BACKGROUND In our previous study, some changes were presented in obstetric care and we studied the morbidity and mortality trends of infants with <500 grams birth weight. Several neonatal protocol changes occurred during the study period. The aim of this study was to analyze the changes in mortality and morbidity of premature infants in light of changing neonatal protocols. MATERIAL AND METHODS We performed a retrospective study of premature infants with <500 grams birth weight, born at our department between 2006 and 2015. We divided the study period into two 5-year epochs and compared mortality and morbidity rates. We calculated the duration of mechanical ventilation and non-invasive respiratory support, and also investigated the potential impact of the differences in clinical practice. RESULTS The survival rate was 30.8% during first epoch, which was significantly lower than the 70.4% survival rate during second epoch. There was no difference in the rate of complications between the 2 epochs. The total number of ventilator and non-invasive ventilation days was significantly lower in the second epoch. CONCLUSIONS We found significant differences in survival rates but no change in the incidence of morbidities between the 2 epochs. Therefore, although the number of neonates surviving with morbidities has increased, so did the number of those with intact survival. The increased survival of infants born with <500 grams birth weight is not associated with increased rate of morbidities. Protocol changes may have contributed to these findings; however, in a retrospective study it is not possible to separate the impact of individual changes.

Efficacy of Prenatal Ultrasound in Craniospinal Malformations According to Fetopathological and Postnatal Neonatological, Pathological Results.

OBJECTIVE: Our objective is to examine the effectiveness of prenatal ultrasound diagnosis of craniospinal malformations compared to postnatal neonatological and pathological findings. METHODS: Over a 7-year period, we preformed approximately 82.500 prenatal ultrasounds of 26.827 pregnancies. We detected 290 fetuses with 351 craniospinal malformations. RESULTS: Craniospinal abnormalities were found as a part of multiplex malformations in 84/290 cases: in 47/84 cases (55.95%) there was complete concurrence between prenatal and postnatal results. In 15/290 fetuses the craniospinal malformation was associated with chromosomal abnormalities. In 9/15 (60%) of these fetuses, malformations were fully diagnosed with ultrasound. Isolated craniospinal malformations occurred in 191/290 cases, in 162/191 (84.82%) the results of prenatal ultrasonography and postnatal or post abortion examinations showed complete concurrence. In addition to the 290 fetuses with craniospinal malformations, there were an additional 17 who were thought by ultrasound to have a craniospinal malformation, which could not be documented after birth (false positives). CONCLUSIONS: Prenatal ultrasound accurately diagnosed 218/290 (75,17%) craniospinal abnormalities, and partially defined the abnormalities in 9.66%, failed to detect abnormalities in 15.17%, with an approximate 0.06% false detection rate.

[The pathogenetic role and expression profile of microRNAs in preeclampsia]. / A mikro-RNS-ek patogenetikai szerepe és expressziós mintázata praeeclampsiában.

Preeclampsia is the leading cause of maternal and fetal morbidity and mortality that affects 3-8% of pregnancies worldwide. Its main symptoms include new onset of high blood pressure and proteinuria after 20 weeks of pregnancy. The cause of the disease is still debated. microRNAs are short, non-coding RNA molecules that play a pivotal part in the posttranscriptional regulation of eukaryotic genes. They are involved in fine-tuning of vital physiological processes such as cell cycle, proliferation, differentiation and cell death. In genomic studies, hundreds of microRNAs were detected in the placenta, which are supposed to regulate placental development and contribute to uncomplicated pregnancy. Several studies have reported changes in the expression of microRNAs in pregnancy. Abnormal microRNA expression may have a role in the development of preeclampsia as it affects the proliferation, migration, and invasion of the trophoblast cells, spiral artery remodeling, and angiogenesis. Some placental microRNAs (e.g., the C19MC microRNA cluster) are able to reach the maternal circulation through their release via exosomes from the trophoblast layer. These 'circulating' microRNA molecules can be applied as biomarkers for the detection of various placental disorders owing to their stability and specificity. Orv Hetil. 2018; 159(14): 547-556.

The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells.

Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First, we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on 12.5 K fraction of PE-EVs: an elevated CD47 "don't eat me" signal (p < 0.01) and decreased exofacial phosphatidylserine "eat-me" signal (p < 0.001) were found along with decreased uptake of these PE-EVs (p < 0.05). The 12.5 K fraction of PE-EVs induced significantly lower chemotaxis (p < 0.01) and cell motility but accelerated cell adhesion of THP-1 cells (p < 0.05). The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia.