Role of CD20 + IL-10 + B-lymphocytes in immunoregulatory processes in women with reccurent miscarriage

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 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 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. 


2021 ◽  
Vol 66 (10) ◽  
pp. 618-622
Author(s):  
A. I. Malyshkina ◽  
N. Y. Sotnikova ◽  
Elena Vladimirovna Grigushkina ◽  
N. V. Kroshkina ◽  
I. E. Talanova

To determine the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, to identify new criteria for predicting abortion before 22 weeks of gestation in women with the threat of early termination and recurrent miscarriage. Materials and methods. A survey of 91 women in the gestation period of 5-12 weeks was carried out. The main group consisted of 59 women with recurrent miscarriage and the threat of early termination at the time of the study. Depending on the outcome of pregnancy, the main group was subdivided into 3 subgroups: subgroup I - 44 women whose pregnancy ended in timely delivery, II - 8 women who had preterm labor, III - 8 women with termination of pregnancy up to 22 weeks ( missed pregnancy or spontaneous miscarriage). The control group consisted of 32 women with uncomplicated pregnancy. The relative content of IL-4 +, IL-6 +, IL-10 +, IFNγ + monocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). In women with threatened early miscarriage and recurrent miscarriage, the percentage of IL-4 + and IL-10 + cells in the population of peripheral monocytes is significantly lower, while IL-6 + cells are higher compared to the control group (p = 0.0001 in in all cases), no statistically significant differences were found in the percentage of IFNγ + cells (p = 0.076). A retrospective analysis revealed that in the group of women with termination of pregnancy up to 22 weeks, there was a significant decrease in IL-10 + monocytes in the peripheral venous blood. Prediction of termination of pregnancy before 22 weeks of gestation is possible with a relative content of IL-10 + monocytes equal to 27.0% or less (sensitivity 87.5%, specificity 95.2%, accuracy 93.1%).


2019 ◽  
Vol 68 (5) ◽  
pp. 63-74
Author(s):  
Anna A. Siniakova ◽  
Elena V. Shipitsyna ◽  
Olga V. Budilovskaya ◽  
Vyacheslav M. Bolotskikh ◽  
Alevtina M. Savicheva

Hypothesis/aims of study. The problem of vaginal infections during pregnancy is of high importance in obstetric practice. To predict the risks and reduce the frequency of pregnancy and childbirth complications, it is necessary to dynamically assess the vaginal microflora and treat its disorders. The aim of the study was to investigate the vaginal microflora and evaluate the effectiveness of treating vaginal infections in pregnant women with a history of miscarriage. Study design, materials and methods. The study included 153 pregnant women in the first trimester. The main group (group I) consisted of 99 women with a history of miscarriage, 35 of whom had signs of threatened abortion (subgroup IA) and 64 did not (subgroup IB). The control group (group II) comprised 54 women without a history of miscarriage and signs of threatened abortion. The vaginal microflora was examined using microscopic, bacteriological and quantitative real-time PCR methods. All patients with an established vaginal infection (bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidiasis) received etiotropic therapy, depending on the microorganisms identified and their sensitivity to antimicrobial drugs. After treatment, in order to assess the effectiveness of the therapy, the vaginal microflora was examined in the second trimester and the outcomes and complications of present pregnancy were evaluated. Results. In women of subgroup IA, vulvovaginitis and bacterial vaginosis were detected 3.5 times more often compared to the control group, and 1.6 times more often compared to subgroup IB (66% and 19%, respectively, p 0.001; 66% and 42%, respectively, p 0.05). Aerobic vaginitis was the most frequent vaginal infection in the first trimester of pregnancy in women of the main group (p 0.05). After treatment, the frequency of the vaginal infections in the second trimester in women of the main group significantly decreased: by 1.9 times in subgroup IA and by 1.5 times in subgroup IB (p 0.05). There were no significant differences in the frequency of adverse pregnancy outcomes in women with bacterial vaginosis or vulvovaginitis as compared to women with normal vaginal microflora. Nevertheless, pregnancy and childbirth complications were diagnosed 4 times more frequently in the main group (23% and 6%, respectively, p 0.05), with the complications occurring significantly more often in the cases of vulvovaginitis or bacterial vaginosis and signs of threatened abortion in the first trimester (p 0.05). Conclusion. Etiotropic therapy of vaginal infections diagnosed in the first trimester of pregnancy in women with a history of miscarriage was highly effective. In 40% of women, vaginal microbiocenosis normalized, and the clinical symptoms of vaginosis/vaginitis disappeared. Differences in the frequency of adverse pregnancy outcomes in women with vulvovaginitis or bacterial vaginosis in the first trimester and in women with normal vaginal microbiocenosis were not significant. However, the treatment of vaginal infections in the group of pregnant women with a history of miscarriage did not significantly affect the frequency of pregnancy and childbirth complications.


GYNECOLOGY ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 18-22
Author(s):  
Nataly I Frolova ◽  
Tatiana E Belokrinitskaya ◽  
Nataliya N Strambovskaya ◽  
Evgeniya P Belozertseva

Aim. To assess the association between polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G and their combinations in patients with recurrent early pregnancy losses (RPL). Materials and methods. This study included two groups of women (age range 20-35 years): 50 currently non-pregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (RPL group), and 50 currently non-pregnant women with a history of having given birth to at least one live baby and without a history of spontaneous abortion, preterm labor, stillbirth, preeclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time. We have analyzed the frequencies, Hardy-Weinberg equilibrium, V-Kramer test, χ2 test, odds ratio (OR) and its 95% confidence interval (95% CI). General (χ2 test, df=2) and multiplicative (χ2 test, df=1) models of inheritance have been used to assess the presence of gene polymorphisms. Results. Significant association between heterozygotes genotype PAI-1-5G4G (72% vs 32%, p=0.000; OR 5.46; 95% CI 2.32-12.87) and RPL was found. Heterozygous genotype FII-20210GA was detected only in RPL group (4% vs 0%). Combinations of genetic polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G increase the risk of RPL by 2.4 times (56% vs 20%; χ2=29.20, р=0.000; OR 3.69, 95% CI 1.52-8.97; strong V-Kramer association). The combination of two heterozygotes variants of minor alleles was found to be a risk factor for RPL (34% vs 10%; χ2=8.73, р=0.004; OR 4.64, 95% CI 1.55-3.84). Combined PAI-1-5G4G + FVL-1691GA genotypes was detected only in RPL group of women (2% vs 0%). No significant association between the combination of three heterozygotes variants of minor alleles and RPL. Conclusion. Our data suggest significant gene-gene interaction of the heterozygotes variants of minor alleles of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G polymorphisms in patients with recurrent miscarriage. Combined genotypes FVL-1691GA/PAI-1-5G4G can be considered as a genetic molecular predictor of recurrent early pregnancy losses.


2010 ◽  
Vol 4 ◽  
pp. CMRH.S5835
Author(s):  
M.N. EL-Gharib ◽  
T.M. Elhawary ◽  
S.H. Elshourbagy ◽  
M.A. Morad

Objective To determine the role of anti-annexin V antibodies (a-A5) as an etiologic factor in recurrent pregnancy failure. Study design Prospective observational study. Material and methods The study included ninety first trimester pregnant women who had a history of unexplained recurrent miscarriage (group I) with ninety well-matched pregnant women with a history of normal reproductive outcome allocated as control group (GII) and another ninety nonpregnant women (GIII). Sera from all women controls were analyzed for anti-annexin antibody measured by Elisa. Results The mean value of a-A5 was 11.37 ± 6.78, 7.7 ± 1.40 and 6.20 ± 0.95 ng/ml in groups I, II and III respectively. There was a significant increase in the mean value a-A5 among women with a history of recurrent miscarriage, compared with controls. The mean value was 13.92 ± 2.42 ng/ml among patients with unfavourable outcome, compared with a corresponding value of 6.95 V 0.58 ng/ml among women with favourable outcome. The receiver operator characteristic curve revealed that the cutoff value of a-A5 was 8.61 ng/ml. Conclusion This study emphasizes the relationship between anti-annexin V antibodies and recurrent miscarriage.


2021 ◽  
Vol 2 ◽  
pp. 42-46
Author(s):  
O.M. Ishak

The objective: to study the features of the course of pregnancy, childbirth and the postpartum period in women with a history of surgical treatment of ovarian apoplexy.Materials and methods. The study involved 62 women in labor (main group, n=62), who were operated on for ovarian apoplexy before pregnancy, and 60 patients in the control group (n=60), who did not have this pathology in the anamnesis. The average age of women was 26,1±2,3 years, the time interval from an episode of ovarian apoplexy to pregnancy was 5,44±2,7 years. Re-apoplexy was observed in 2 cases (3,22%).Results. The study found that the main complication in the first trimester of pregnancy was reproductive loss, mainly in the form of a stillborn pregnancy. In the early stages of gestation, the threat of abortion was 3 times more often observed in the main group than in the control group. In the second trimester draws attention to several facts of complications that are characteristic of patients in the main group: the widespread prevalence of acute or chronic infectious pathology in the acute stage (51,6% vs. 11,7% in the control group), the development of preeclampsia 2 times more often among pregnant women with ovarian apoplexy (38,7% vs. 20,0%), as well as mild anemia (40,3% vs. 21,6%).The results of the study indicate a high frequency of premature ejaculation of amniotic fluid in pregnant women with ovarian apoplexy (29,0% vs. 13,3%), rapid labor (16,1% vs. 1,7%), umbilical cord entanglement (33,9% vs. 15,0%), hypotonic bleeding in the early postpartum period (14,5% vs. 1,67%). The frequency of cesarean section did not differ significantly in both groups (p>0,05). The assessment of newborns on the Apgar scale had no statistically significant differences.Conclusion. Pregnant women who have a history of surgical treatment of ovarian apoplexy are at risk for developing early miscarriage, complicated gestation, childbirth and the postpartum period. Analysis of the reproductive function of women in the study groups reflected the problems of gestation mainly in the early stages in the form of reproductive loss or symptoms of miscarriage, in the late stages of pregnancy complications were mainly due to extragenital pathology. The data obtained during the study in practice should contribute to the development of rehabilitation measures and pre-pregnancy training, which are aimed at restoring reproductive health and prevention of complications of pregnancy and childbirth in women at risk.


Author(s):  
O.M. Perkhulyn

Introduction. Today, the frequency of infertility is increasing worldwide. Infertility, associated with anovulation, is especially challenging for the medical correction especially. The leading aspect of this problem is hormonal disorders in the body of a woman. The aim of this study was to assess the level of estradiol and progesterone in the blood serum of pregnant women with cervical insufficiency and infertility associated with anovulation in the history. Materials and methods. The main group included 30 pregnant women with the II trimester of pregnancy, who had cervical insufficiency and infertility associated with anovulation in the past medical history. They got pregnant after assisted reproductive technologies. The control group included 30 pregnant women without cervical insufficiency and with physiological gestation. Estradiol and progesterone levels in blood serum were determined at 20-22 and 30-32 weeks of gestation. Results. The average age of the women in the basic group was statistically higher relative to the control one – 31.30±1.16 and 27.30±0.92 years, respectively (p=0.02). There was no difference in the number of pregnancies in women between both groups. In the main group, 73.33% of the persons were primagravida, 10.00 % of patients had two pregnancies, and 16.67 % - three pregnancies. 56.67 % of the women in the control group were primagravida, 26.67 % had two pregnancies, 16.66 % - three pregnancies. Although primaparas predominated in both groups, the number of such women was in 1.47 times higher in the main group (93.33 %) than in control (63.33 % of patients; χ2=6.28, p=0.01); 6.67 % and 26.67 % women had two labors respectively and 10.00 % of healthy patients - three labors. The concentration of estradiol at the 20-22 and 30-32 weeks of pregnancy in women of the main group almost corresponded to physiological parameters. However, the progesterone level in women with cervical insufficiency and a history of infertility was by 13.44 % lower than in healthy pregnant women at 20-22 weeks, and by 17.02% at 30-32 weeks (p=0.003). Conclusions. In pregnant women with cervical insufficiency and infertility associated with anovulation, the level of estradiol in the II and III trimesters of gestation mainly corresponds to the level of physiological pregnancy. However, they have the decrease in progesterone concentration in the III trimester of pregnancy relative to healthy pregnant women (p<0.003).


2018 ◽  
Vol 30 (1) ◽  
pp. 49-55
Author(s):  
Sharmin Sultana ◽  
Mosammat Nargis Shamima ◽  
Sahela Jesmin ◽  
Nargis Zahan ◽  
Md Abu Zahid ◽  
...  

This was a hospital based case control study. The study included patients attending in outdoor and indoor Department of Obstetrics and Gynaecology of Rajshahi Medical College, Hospital since July 2014 to June 2016. The aim of this study was to determine thyroid antibodies is a risk factor for recurrent pregnancy loss. Sixty seven pregnant or non pregnant women with history of recurrent miscarriage during 1st trimester were selected as case group and another sixty seven pregnant women who reached their 12 weeks uneventfully with no history of recurrent miscarriage were selected as control group. Patients with other cause of recurrent miscarriage such as metabolic or endocrinologic disorders, genital organ anomaly, uterine fibroid were excluded from the study. Thyroid function test and thyroid antibodies (FT4, TSH and TPO-Ab) were measured for the two groups. The result of this study showed that the percentage of positive TPO-Ab in target and control group is 67.16% and 5.95% respectively. The study observed that the mean serum concentrations of FT4 in the control subject was significantly higher than the mean of the target group (p-value <0.05). The TSH concentration was increased in miscarriage women with positive antibodies compared with the concentration of TSH in the control group with positive antibodies. The conclusions are that there is a deficiency in thyroid hormones or thyroid’s functional capacity is unable to meet the extra demands of pregnancy which may be one of the causes of recurrent miscarriage. Moreover positive thyroid antibodies pregnant women can reach term and have babies when the concentration of TSH is low during the first trimester, so the risk of miscarriage could be high in positive thyroid antibodies.TAJ 2017; 30(1): 49-55


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