scholarly journals REGULATION OF PERIPHERAL B-LYMPHOCYTE DIFFERENTIATION IN RECURRENT MISCARRIAGE

2021 ◽  
Vol 23 (4) ◽  
pp. 711-716
Author(s):  
A. I. Malyshkina ◽  
N. Yu. Sotnikova ◽  
A. V. Kust ◽  
D. N. Voronin

The important role of immune disorders in recurrent miscarriage has been proven. Clarification of the character of B-lymphocyte differentiation and its regulation factors in women with threatened miscarriage and recurrent miscarriage in history is an urgent problem, since it will reveal the immune mechanisms of the pathogenesis of this pathology. Purpose: to establish the features of B-lymphocyte differentiation and factors of its regulation in women with a history of recurrent miscarriage and threatening spontaneous miscarriage at the time of examination.Were examined pregnant women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 60 pregnant women with a threatening spontaneous miscarriage at the time of examination and a history of recurrent miscarriage. As a control, 35 pregnant women with uncomplicated pregnancy were examined. The comparison group consisted of 25 primary pregnant women with threatened spontaneous miscarriage at the time of examination. The material for the study was peripheral venous blood. Subpopulations of B-lymphocytes CD19+, CD19+ IgD+, CD20+IgM+, CD20+IgG+ were determined by flow cytometry; CD19+CD20- CD38+, CD19+CD27- , CD19+CD27+. Serum levels of BAFF and APRIL were assessed by enzyme-linked immunosorbent assay.In the main group, an increase in the proportion of B-cells, CD20+IgM+-lymphocytes and memory cells was recorded in the peripheral blood, along with a decrease in the level of naive cells and plasma cells. In the comparison group, an increase in the proportion of immature IgM+B-cells, circulating memory cells, along with a decrease in naive B-lymphocytes, was registered. in the main group there was a pronounced decrease in the serum BAFF level compared with the control and comparison groups. Analysis of the APRIL content showed a pronounced downward trend in groups with threatened miscarriage relative to healthy pregnant women. Thus, threatening habitual and sporadic miscarriages were associated with a shift in the differentiation of B-lymphocytes towards immature forms and a lack of regulatory influence of BAFF and APRIL, which is reflected in the disruption of B-cell homeostasis and weakening of humoral effector mechanisms at the systemic level. The revealed changes may indicate a single mechanism for the development of a threatening spontaneous miscarriage, the severity of which increases with repeated loss of pregnancy. These changes can lead to an increase in effector cytotoxic mechanisms and an increase in proinflammatory cytokines, which can lead to the development of damaging reactions in the fetoplacental complex, which can be reflected in the clinical picture of the threat of termination of pregnancy. 

2021 ◽  
Vol 66 (8) ◽  
pp. 485-488
Author(s):  
A. V. Kust ◽  
N. Y. Sotnikova ◽  
A. I. Malyshkina ◽  
D. N. Voronin

To determine the level of CD20 + IL-10 + B-lymphocytes in pregnant women with the threat of termination of pregnancy at 5-12 weeks and recurrent miscarriage in history and compare the data obtained with the end of gestation. A survey of 65 women at a gestational age of 5-12 weeks was carried out. The main group consisted of 33 women with a threatening recurrent miscarriage at the time of the examination, the comparison group consisted of 10 pre-pregnant women with a threatening sporadic miscarriage at the time of the examination, the control group consisted of 22 pregnant women without signs of a threatening miscarriage. The main group, depending on the outcomes of pregnancy, is divided into 2 subgroups: subgroup A - pregnancy ended in undeveloped pregnancy or miscarriage (9 women), subgroup B - pregnancy ended in childbirth (24 women). The relative content of CD20 + IL-10 + B-lymphocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). Women in the main group had a significantly lower level of CD20 + IL-10 + B-lymphocytes in comparison with the rest of the surveyed. A retrospective analysis revealed that among women of subgroup A there was a sharp decrease in CD20 + IL-10 + cells compared with subgroup B. Prediction of a non-developing pregnancy and spontaneous miscarriage up to 22 weeks of gestation in pregnant women with threatened spontaneous miscarriage and a history of recurrent miscarriage is possible with the relative content of CD20 + IL-10 + equal to or less than 4.5% (sensitivity 100%, specificity 82.6%, accuracy 87.9%).


2021 ◽  
Vol 70 (4) ◽  
pp. 73-79
Author(s):  
Anna I. Malyshkina ◽  
Natalia Y. Sotnikova ◽  
Dmitriy N. Voronin ◽  
Alena V. Kust

BACKGROUND:The frequency of recurrent miscarriage is up to 5 % of all desired pregnancies and is mainly due to immunological disorders. Dysfunction in the regulation of the functional activity of B lymphocytes is the pathogenetic link in multiple obstetric complications, including habitual miscarriage. AIM:The aim of this study was to characterize the regulation of the functional activity of peripheral B lymphocytes in pregnant women with threatened spontaneous miscarriage and a history of habitual miscarriage. MATERIALS AND METHODS:We examined 88 women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 36 patients with threatened spontaneous miscarriage at the time of examination and a history of habitual miscarriage. The control group included 28 women with uncomplicated pregnancy. The comparison group consisted of 24 primary pregnant patients with threatened spontaneous abortion at the time of examination. BAFF and APRIL levels in the blood serum were determined by enzyme immunoassay. The content of CD19+BAFFR+B lymphocytes in the lymphocyte gate was evaluated in the peripheral blood by flow cytometry using monoclonal antibodies. Akt mRNA expression was assessed using real-time reverse-transcription quantitative polymerase chain reaction. CD19+В lymphocytes were isolated by direct magnetic separation. RESULTS:In the main group, there was an increase in expression of BAFF receptors on peripheral CD19+B lymphocytes and a decrease in the serum BAFF concentration compared to the parameters in the other study groups. We also found a pronounced trend towards a decrease in the serum APRIL level in the main and comparison groups of patients compared to healthy pregnant women. Besides, Akt mRNA expression in peripheral CD19+B lymphocytes was increased in the main group. CONCLUSIONS:Threatened habitual abortion is associated with the deficit of the regulatory influence of BAFF and APRIL, which is expressed in the disruption of B cell homeostasis and the weakening of humoral effector mechanisms.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanglin Wu ◽  
Songying Zhang ◽  
Xiaona Lin ◽  
Jing He ◽  
Shasha Wang ◽  
...  

Abstract Background Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. Methods Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42–0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40–0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79–1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34–0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. Conclusion Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.


2021 ◽  
Vol 23 (4) ◽  
pp. 755-760
Author(s):  
E. V. Grigushkina ◽  
N. Yu. Sotnikova ◽  
N. V. Kroshkina ◽  
A. I. Malyshkina ◽  
I. E. Talanova

Currently, in the pathogenesis of recurrent miscarriage, a special role is given to immunological factors, in particular the role of innate immunity. The aim of the study was to assess the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, as well as to identify new criteria for predicting the outcome of pregnancy in women with the threat of early termination and recurrent miscarriage. Materials and methods. 88 pregnant women at 5-12 weeks’ gestation were examined, the main group consisted of 59 women with recurrent miscarriage and threatened miscarriage at the time of the study, the control group – 29 women with uncomplicated pregnancy without recurrent miscarriage. The main group, depending on the outcomes of pregnancy, was subdivided into subgroups: subgroup I – 42 women whose pregnancy ended in timely delivery, subgroup II – 8 women with preterm labor, subgroup III – 9 women with abortion up to 22 weeks (spontaneous miscarriage and non-developing pregnancy). In the control group, all women had a timely delivery. Research material – peripheral venous blood. The relative content of IL-4+, IL-6+, IL-10+, IFNγ+ monocytes was assessed on a FACSCanto II flow cytometer using monoclonal antibodies. Statistical data processing was carried out using a package of standard applied programs. Results. In the group of women with recurrent miscarriage and threatened miscarriage, the relative content of IL-10+ and IL-4+ monocytes was reduced and the content of IL-6+ monocytes was increased compared to the control group (p = 0.0001 in all cases). There were no statistically significant differences in the content of IFNγ+ monocytes in the compared groups (p = 0.069). With a relative content of IL-4+ monocytes equal to 26.7% or less, preterm labor is predicted. With a relative content of IL-10+ monocytes equal to 27.0% or less, abortion (spontaneous miscarriage or miscarriage) is predicted in gestational age up to 22 weeks. An increase in the ratio of IFNγ+/ IL-4+, IFNγ+/IL-10+, IL-6+/IL-4+, IL-6+/IL-10+ monocytes was found in the main group (p < 0.0001 in all cases ). Conclusions. In women with recurrent miscarriage in all subgroups, the level of M1 monocytes prevailed over the level of M2 monocytes. The data obtained allowed the development of new prognostic criteria for termination of pregnancy up to 22 weeks and premature birth. 


2018 ◽  
pp. 118-121
Author(s):  
L.M. Vygivska ◽  
◽  
I.A. Usevych ◽  
I.V. Maidannyk ◽  
V.F. Oleshko ◽  
...  

The article represents the results of a prospective clinical and paraclinical examination of women with a history of infertility, pregnancy in which occurred as a result of the assisted reproductive technologies application. The objective: was to study the dynamics of pregnancy features of the psycho - emotional state and the concentration of stress-associated hormones in the serum of pregnant women after the application of assisted reproductive technologies in order to improve the tactics of antenatal care and prevention of obstetric and perinatal complications. Materials and methods. The main group consisted of 80 pregnant women with endocrine infertility, in which pregnancy occurred as a result of therapeutic cycles of ART, control – 50 first-pregnant women with spontaneous fertilization, taken in an arbitrary order of clinical, statistical and laboratory and instrumental studies. In pregnant women of the study groups, in order to determine the psycho emotional state in the screening mode, a clinical interview was conducted by filling out questionnaires that contained the Spilberger test questions in modification of Y.L. Hanina and «Test of relationof pregnant» by the method of I.V. Dobryakova. In the dynamics of pregnancy, the concentration of prolactin (PRL) and cortisol (K) was determined by the enzyme immunoassay on the Reader-MSR-1000 apparatus using test systems manufactured by Hema-Medicament (Russia). Results. Pregnant women with infertility in past history were characterized by a state of chronic stress. According to the results of the Spielberger test in modification Y .L. Hanina every second pregnant of main group had a high level of reactive and every fourth personal anxiety. Almost 90.0% of pregnant women after art are characterized by the presence of pathological PKGD, among which an alarming and depressive type was registered in every sixth and twelfth pregnant woman, respectively. The obtained data are confirmed by the results of the study of the level of K and PRL. For women with a history of infertility and pregnancy, which is the result of therapeutic cycles of ART, inherent in increasing concentrations of stress-associated hormones – cortisol and prolactin, which is one of the reasons for the complicated course of pregnancy and requires reasonable pathogenetic correction. Conclusion. For women who are pregnant as a result of the use of therapeutic cycles of art characterized by a high level of personal and reactive anxiety and PKGD, which confirm the presence of neuropsychiatric and afferent disorders. Increasing the concentration of stress-associated hormones is one of the causes of complicated pregnancy and requires a reasonable pathogenetic correction. Key words: pregnancy, infertility, assisted reproductive technologies, psychological status, cortisol, prolactin.


2019 ◽  
pp. 184-190
Author(s):  
E. F. Khamidullina ◽  
L. Yu. Davidyan ◽  
D. R. Kasymova ◽  
A. Yu. Bogdasarov

The purpose and objectives of the study is to identify the hormonal, biochemical and ultrasound features of the gestation course in women with beneficial tumours of the uterus. Results. We conducted a complete clinical examination and prospective observation of 182 pregnant women. Of which, 98 puerperas with a verified diagnosis of uterine fibroids and/or endometriosis, which developed before gestation, but did not prevent the onset of pregnancy, were included into the main group. The comparison group included 84 women with physiological pregnancy. The studies showed that 14 pregnant women in the main group had C677T (Ala222Val) T/T mutation, while only 2 women in the comparison group had a decrease in enzyme activity due to genetic mutation. Accordingly, the homocysteine level was almost 3 times lower in the comparison group than in the main group. The women with hyperhomocisteinemia (HHC) and uterine fibroid in the main group showed the lowest estriol level and hCG level, while women without HHC had higher estriol level and hCG levels. It was found that almost all patients with HHC had subclinical hypothyroidism. Ultrasound imaging and biochemical tests at the beginning of the 2nd trimester: no ultrasound markers of fetal anomalies were identified in women from both groups; however, signs of retrochorial hematoma were detected in 57 women from the main group, which was confirmed by clinical manifestations and previous ultrasound imaging in earlier gestation periods. Conclusion. Thus, placenta formation in women with HHC and uterine fibroids is accompanied by relative hormonal insufficiency, which is clinically manifested as a threat of miscarriage in the early stages, but carrying a child is possible due to appropriate management of a patient as part of the preserving therapy. However, the issue of preventing the development of fetoplacental insufficiency is a valid one for further investigation.


2007 ◽  
Vol 204 (3) ◽  
pp. 645-655 ◽  
Author(s):  
Menno C. van Zelm ◽  
Tomasz Szczepański ◽  
Mirjam van der Burg ◽  
Jacques J.M. van Dongen

The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.


2018 ◽  
Vol 10_2018 ◽  
pp. 106-111 ◽  
Author(s):  
Solovyeva A.V. Solovyeva ◽  
Gerasimova O.P. Gerasimova ◽  
Ermolenko K.S. Ermolenko ◽  
Gevorgyan D.A. Gevorgyan ◽  
◽  
...  

Author(s):  
Rhoda Wilson ◽  
Carol Jenkins ◽  
Helen Miller ◽  
Iain B McInnes ◽  
Judith Moore ◽  
...  

2018 ◽  
Vol 24 (2) ◽  
Author(s):  
Nataliya Henyk ◽  
Nataliya Yakumchuk

 The study of the influence of the autonomic nervous system on the course of pregnancy, childbirth and fetal state remains relevant. Changes in the parameters of electroencephalography may be detected long before the onset of clinical symptoms in the complicated course of pregnancy.  The objective of the research was to evaluate electroencephalography in women with placental dysfunction and gestational complications taking into account the type of psychological component of gestation dominant.  Materials and methods. Electroencephalography was performed in 60 pregnant women at the age of 19 to 45 years with gestational hypertension and fetal distress during pregnancy. The main group included 40 patients, who were stratified according to the type of psychological component of gestation dominant: 10 patients with euphoric type, 20 pregnant women with anxious and depressive type, 10 patients with hypogestognostic type. The comparison group comprised 20 patients with optimal type of psychological component of gestation dominant and normal course of the first half of pregnancy. The assessment of psychological component of gestation dominant was carried out according to the method proposed by Dobriakov I.V. - "Pregnant woman attitude test". Registrations, spectral and coherent analysis of electroencephalography were performed using BrainTest-24 hardware and software complex.  \textbf{Results and discussion. }Electroencephalography of the patients of the comparison group was in line with current concepts regarding the physiological norm. In the main group, there were the following changes in electroencephalography: non-sinusoidal forms of alpha-oscillations (77.5%), high index of fast rhythms, flashes of spike waves under load, disturbances of the frontal occipital gradient with the focus on the anterior sections of the hemispheres.  Conclusions. The use of electroencephalography in women with different types of psychological component of gestation dominant in case of progressive placental dysfunction and preeclampsia on its background allows identifying characteristic changes, modifying the program of therapeutic measures, differentiating obstetric tactics and terms of delivery.


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