FEATURES OF MONOCYTE POLARIZATION AT DIFFERENT OUTCOMES IN WOMEN WITH RECURRENT MISCARRIAGE

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.

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Рrediction of the outcome of pregnancy in women with reccurent miscarriage

Russian Clinical Laboratory Diagnostics ◽

10.51620/0869-2084-2021-66-10-618-622 ◽

2021 ◽

Vol 66 (10) ◽

pp. 618-622

Author(s):

A. I. Malyshkina ◽

N. Y. Sotnikova ◽

Elena Vladimirovna Grigushkina ◽

N. V. Kroshkina ◽

I. E. Talanova

Keyword(s):

Recurrent Miscarriage ◽

Venous Blood ◽

Main Group ◽

Relative Content ◽

Termination Of Pregnancy ◽

Early Termination ◽

Control Group ◽

Becton Dickinson ◽

Uncomplicated Pregnancy ◽

Timely Delivery

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%).

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

Russian Clinical Laboratory Diagnostics ◽

10.51620/0869-2084-2021-66-8-485-488 ◽

2021 ◽

Vol 66 (8) ◽

pp. 485-488

Author(s):

A. V. Kust ◽

N. Y. Sotnikova ◽

A. I. Malyshkina ◽

D. N. Voronin

Keyword(s):

Pregnant Women ◽

B Lymphocytes ◽

Recurrent Miscarriage ◽

Sharp Decrease ◽

Main Group ◽

Relative Content ◽

Control Group ◽

Becton Dickinson ◽

Spontaneous Miscarriage ◽

History Of

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%).

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Regulation of the functional activity of peripheral B lymphocytes in pregnant women with a history of recurrent miscarriage

Journal of obstetrics and women s diseases ◽

10.17816/jowd62675 ◽

2021 ◽

Vol 70 (4) ◽

pp. 73-79

Author(s):

Anna I. Malyshkina ◽

Natalia Y. Sotnikova ◽

Dmitriy N. Voronin ◽

Alena V. Kust

Keyword(s):

Pregnant Women ◽

Mrna Expression ◽

B Lymphocytes ◽

Functional Activity ◽

Recurrent Miscarriage ◽

Quantitative Polymerase Chain Reaction ◽

Main Group ◽

Control Group ◽

Spontaneous Miscarriage ◽

History Of

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.

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NEW EARLY PROGNOSTIC CRITERIA FOR PREGNANCY OUTCOME IN WOMEN WITH RECURRENT MISCARRIAGE

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2020-65-5-294-298 ◽

2020 ◽

Vol 65 (5) ◽

pp. 294-298

Author(s):

N. Yu. Borzova ◽

N. I. Ivanenkova ◽

N. Yu. Sotnikova ◽

A. I. Malyshkina

Keyword(s):

Premature Birth ◽

Recurrent Miscarriage ◽

Venous Blood ◽

Memory Cells ◽

Color Flow ◽

Adequate Treatment ◽

Spontaneous Miscarriage ◽

Habitual Abortion ◽

New Criteria ◽

Timely Delivery

To determine the new criteria for predicting the outcome of pregnancy in women with habitual abortion based on features of differentiation of naive T cells and memory cells in a population of T-helper (CD4+) and cytotoxic T lymphocytes (CD8+). The study involved 61 women with threatened and habitual abortion in the first trimester of gestation. Depending on the outcome of pregnancy was allocated to 3 groups: I went to 39 women whose pregnancy ended in timely delivery; in II - 10 women whose pregnancies ended in premature birth; in III - 11 patients in whom there was a spontaneous miscarriage. Using three-color flow cytometry as peripheral venous blood in populations of CD8+ and CD4+ determined by the content Tn, Tcm, Tem and Temra cells. Statistical analysis was carried out in the program «MicrosoftOffice 2010», «Statistica for Windows 6.0» and MedCalc». When conducting a retrospective assessment, it was found that in the group of patients whose pregnancy ended in preterm delivery, the percentage of CD4 + Tem memory cells was significantly higher and CD4 + Tn lower than in the subgroup with timely delivery (p = 0.013 and p = 0.025, respectively ) In patients with early spontaneous miscarriage, the level of CD8 + Tn significantly decreased against the background of the growth of CD8 + Tem memory cells compared with the same parameters in patients with timely delivery (p = 0.040 and p = 0.014, respectively). Prediction of spontaneous abortion is possible up to CD4+ Tn equal to 34.2% or less (sensitivity - 100.0%, specificity - 56.4%, accuracy - 63.8%), premature birth - if the CD4+ Tn equal to 35, 2% or less (sensitivity - 66.7%, specificity - 74.4% accuracy - 72.9%). Thus, the new criteria will allow additional time to identify risk and assign adequate treatment aimed at prolonging the desired pregnancy.

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REGULATION OF PERIPHERAL B-LYMPHOCYTE DIFFERENTIATION IN RECURRENT MISCARRIAGE

Medical Immunology (Russia) ◽

10.15789/1563-0625-rop-2295 ◽

2021 ◽

Vol 23 (4) ◽

pp. 711-716

Author(s):

A. I. Malyshkina ◽

N. Yu. Sotnikova ◽

A. V. Kust ◽

D. N. Voronin

Keyword(s):

Pregnant Women ◽

B Lymphocytes ◽

B Lymphocyte ◽

Comparison Group ◽

Recurrent Miscarriage ◽

Main Group ◽

Lymphocyte Differentiation ◽

Spontaneous Miscarriage ◽

Threatened Miscarriage ◽

History Of

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.

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Great Obstetrical Syndromes In G20210a Mutation Carriers Associated With High Prothrombin Activity

10.21203/rs.3.rs-67776/v1 ◽

2020 ◽

Author(s):

Mariya Nikolaeva ◽

Andrey Pavlovich Momot ◽

Marina Sabirovna Zainulina ◽

Natalia Nikolaevna Yasafova ◽

Irina Alekseevna Taranenko

Keyword(s):

Blood Plasma ◽

Venous Blood ◽

Threshold Value ◽

Main Group ◽

Trophoblast Invasion ◽

Control Group ◽

G20210a Mutation ◽

Factor Ii ◽

Invasion Waves ◽

In Blood Plasma

Abstract Objective: to study the association between high activity of Factor II (prothrombin) in blood plasma with G20210A mutation and the development of great obstetrical syndromes.Material and methods: A prospective clinical cohort study was conducted on 290 pregnant women (average age 31.7±4.7 years old). The main group was made up of 140 G20210A patients, while the control group comprised 150 women with the wild G20210G type. The aim was to evaluate the activity of Factor II in the venous blood plasma during the stages of pregnancy with regard to trophoblast invasion waves. As per results, association analysis of Factor II activity value and gestational complications was carried out.Results: In the control group, the median (Me) of Factor II activity ranged from 108% (preconception period) to 144% (pregnancy) [95% CI 130-150]. In patients with the GA type, the value was significantly higher in related periods, ranging from 149% to 181% [95% CI 142-195], p<0.0001. With Factor II activity ranging from 148.5% to 180.6%, pregnancies in the main group had no complications. Higher levels of Factor II activity were associated with the development of early and/or severe preeclampsia (PE) and fetal growth retardation (FGR).Conclusion: The data obtained regarding Factor II activity in blood plasma, juxtaposed with the development of great obstetrical syndromes, allow to assume that manifestation of G20210A in early and/or severe PE and FGR is associated with this coagulation factor's level of activity. Threshold value of the Factor II activity with G20210A mutation, allowing to predict the development of PE, comprised 171.0% at the preconception stage (AUC – 0.86; p<0.0001) and within 7-8 weeks of gestation it was 181.3% (AUC – 0.84; p<0.0001).

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Vaginal and intestinal microbiocenosis composition in pregnant women

Journal of obstetrics and women s diseases ◽

10.17816/jowd68629-36 ◽

2020 ◽

Vol 68 (6) ◽

pp. 29-36

Author(s):

Alexandr A. Bezmenko ◽

Natalya D. Sadovaya

Keyword(s):

Pregnant Women ◽

Normal Pregnancy ◽

Main Group ◽

Control Group ◽

Microbiological Analysis ◽

Control Groups ◽

Threatened Miscarriage ◽

Intestinal Dysbiosis ◽

Grade Ii ◽

And Control

Hypothesis/aims of study. It is assumed that intestinal dysbiosis, as well as bacterial vaginosis, may be one of the risk factors, and in some cases, the direct cause of pregnancy complications. This study was aimed to assess the intestinal and vaginal microbiocenosis composition in women with threatened miscarriage and normal pregnancy. Study design, materials and methods. The study involved 68 women aged 18 to 35 years (mean age 27.6 0.7 years) in pregnancy from 6 to 18 weeks. The main group consisted of 38 women with threatened miscarriage. The control group included women (n = 30) with normal pregnancy. Patients of the main and control groups were examined in accordance with the requirements of the Ministry of Health order No. 572n. In addition, a qualitative and quantitative microbiological analysis of vaginal discharge and feces was performed using the real-time polymerase chain reaction method. Results. Vaginal dysbiosis was detected in 60.5% of pregnant women of the main group and only 13.3% of women of the control group. In the main group, grade II dysbiosis was found in 23.7% of cases, and grade I dysbiosis in 36.8% of cases, while in the control group, these grades were found only in 3.3% and 10% of cases, respectively. Intestinal dysbiosis was diagnosed in 100% of the examined pregnant women. In patients of the main group, intestinal dysbiosis was detected as follows: grade I in 29% of cases, grade II in 52.6% of cases, and grade III in 18.4% of cases. In patients of the control group, the disorders corresponded mainly to grade I (83.4%) and, to a lesser extent, grade II (16.6%) dysbiosis, there being no cases of severe dysbiosis revealed. Conclusion. Women with threatened miscarriage had the most pronounced dysbiotic changes in vaginal and intestinal microflora compared to the control group. Vaginal dysbiosis was combined with intestinal dysbiosis in 100% of cases in patients of the main and control groups, and the degree of dysbiotic changes in the vaginal microflora was directly proportional to the degree of intestinal dysbiosis.

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Cytokine profile in women with threatened miscarriage and intestinal dysbiosis

Journal of obstetrics and women s diseases ◽

10.17816/jowd48554 ◽

2021 ◽

Vol 70 (1) ◽

pp. 51-58

Author(s):

Alexander A. Bezmenko ◽

Natalia D. Sadovaya ◽

Marina E. Meshkova ◽

Elena A. Malakhova

Keyword(s):

Pregnant Women ◽

Intestinal Microflora ◽

Main Group ◽

Control Group ◽

Endotoxin Level ◽

Threatened Miscarriage ◽

Intestinal Dysbiosis ◽

Grade Ii ◽

Pro Inflammatory Cytokines ◽

Intestinal Microbiocenosis

Hypothesis/Aims of study: Systemic endotoxinemia resulting from intestinal dysbiosis activates the Th1 immune response and excessive production of proinflammatory cytokines, which can cause abortion. This study was aimed at assessing interleukin levels in women with the threat of miscarriage and exploring their dependence on intestinal microbiocenosis and the level of endotoxinemia. Study design, materials and methods: The study involved 87 women aged 18 to 43 years in pregnancy from six to 22 weeks. The main group consisted of 50 women with a threatened miscarriage. The control group included 37 women with normal pregnancy. A qualitative and quantitative analysis of intestinal microbiocenosis was performed by real-time PCR, with endotoxin and interleukin levels evaluated using conventional methods. Results: In patients of the main group, intestinal dysbiosis of grade I was detected in 30 % (n = 15), of grade II in 46 % (n = 23), and of grade III in 24 % (n = 12) of cases. In the control group, intestinal microflora disorders corresponded to grade I dysbiosis in 67.6 % (n = 25) and grade II dysbiosis in 32.4 % (n = 12) of cases, there being no cases of severe dysbiosis revealed. The level of endotoxin in pregnant women of the main group was 0.57 0.02 nmol / ml and was classified as increased. The endotoxin level in the blood serum of pregnant women of the control group was 0.34 0.02 nmol / ml and was characterized as low (p 0.001). A strong correlation was found (r = 0.8, p 0.001) between the grade of intestinal dysbiosis and the level of endotoxinemia. The cytokine profile in patients of the main group was characterized by increased concentrations of pro-inflammatory cytokines (IL-1 4.9 1.6 pg / ml, IL-6 4.8 1.5 pg / ml) and a decreased concentration of anti-inflammatory cytokine (IL-10 18.0 4.5 pg / ml), when compared to the control group (IL-1 1.8 0.2 pg / ml, IL-6 2.1 0.2 pg / ml, IL-10 30.3 4.4 pg/ml). There were a statistically significant moderate positive correlation between the level of endotoxinemia and the concentration of pro-inflammatory cytokines and a weak negative correlation between the endotoxin level and the concentration of anti-inflammatory IL-10. Conclusion: Endotoxinemia, which occurs as a result of intestinal microflora dysbiosis and activates pro-inflammatory pathways, can really be as a triggering factor in the pathogenesis of miscarriage in pregnant women.

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Pregnancy complications in G20210A mutation carriers associated with high prothrombin activity

Thrombosis Journal ◽

10.1186/s12959-021-00289-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

M. G. Nikolaeva ◽

A. P. Momot ◽

M. S. Zainulina ◽

N. N. Yasafova ◽

I. A. Taranenko

Keyword(s):

Blood Plasma ◽

Venous Blood ◽

Threshold Value ◽

Main Group ◽

Trophoblast Invasion ◽

Control Group ◽

G20210a Mutation ◽

Factor Ii ◽

Invasion Waves ◽

In Blood Plasma

Abstract Objective To study the association between high activity of Factor II (prothrombin) in blood plasma with G20210A mutation and the development of great obstetrical syndromes. Material and methods A prospective clinical cohort study was conducted on 290 pregnant women (average age 31.7 ± 4.7 years old). The main group was made up of 140 G20210A patients, while the control group comprised 150 women with the wild G20210G type. The aim was to evaluate the activity of Factor II in the venous blood plasma during the stages of pregnancy with regard to trophoblast invasion waves. As per results, association analysis of Factor II activity value and gestational complications was carried out. Results In the control group, the median (Me) of Factor II activity ranged from 108% (preconception period) to 144% (pregnancy) [95% CI 130–150]. In patients with the GA type, the value was significantly higher in related periods, ranging from 149 to 181% [95% CI 142–195], p < 0.0001. With Factor II activity ranging from 148.5 to 180.6%, pregnancies in the main group had no complications. Higher levels of Factor II activity were associated with the development of early and/or severe preeclampsia (PE) and fetal growth retardation (FGR). Conclusion The data obtained regarding Factor II activity in blood plasma, juxtaposed with the development of great obstetrical syndromes, allow to assume that manifestation of G20210A in early and/or severe PE and FGR is associated with this coagulation factor’s level of activity. Threshold value of the Factor II activity with G20210A mutation, allowing to predict the development of PE, comprised 171.0% at the preconception stage (AUC – 0.86; p < 0.0001) and within 7–8 weeks of gestation it was 181.3% (AUC – 0.84; p < 0.0001).

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Associations of SNP rs_7927894 of FLG gene and TARC/CCL17 with atopic dermatitis in children

Modern pediatrics. Ukraine ◽

10.15574/sp.2021.118.12 ◽

2021 ◽

pp. 12-18

Author(s):

V.O. Dityatkovsky ◽

◽

O.E. Abaturov ◽

N.V. Naumenko ◽

O.O. Alifirenko ◽

...

Keyword(s):

Atopic Dermatitis ◽

Statistical Significance ◽

Venous Blood ◽

Clinical Signs ◽

Main Group ◽

Control Group ◽

Serum Concentrations ◽

Control Groups ◽

And Control ◽

Severity Degree

One of the main genetic factors of the development of atopic dermatitis (AD) in children are single nucleotide polymorphisms (SNP) of the filagrin gene (FLG), particularly rs_7927894 FLG. One of the mostly studied and promising AD marker chemokines (CK) is the thymusE and activation regulated chemokine (TARC/CCL17). Purpose – to detect the associations and role of different variants of SNP rs_7927894 FLG gene and TARC/CCL17 in children suffering different AD clinical proE files (CP) – isolated or combined with comorbid atopic disorders (AtD). Materials and methods. The main group comprised 39 patients aged 3 to 18 years, suffering the isolated AD or combined with comorbid AtD. The control group comprised 47 patients aged 3 to 18 years, suffering the pathology of gastrointestinal tract without clinical signs of atopy. All the patients of the main and control groups had undergone detection of the genotype variants of SNP rs_7927894 FLG gene by real-time polymerase chain reaction and detection of TARC/CCL17 serum concentrations in venous blood. The cutEoff value of statistical significance was set as p<0.05. Results. The incidence and association of genotype variants C/C, C/T and T/T SNP rs_7927894 FLG gene in patients of cohorts of the studied groups were detected as follows: C/T rs_7927894 FLG was significantly the most common in the general main group (56.4%, p<0.05), within the cohort of CP AD isolated (61.1%, p<0.05) and CP of AD combined with comorbid AtD (52.4%, p<0.05). There were detected the associations of studied SNP with AD: C/T rs_7927894 FLG is significantly directly associated with AD (r=0.291, p<0.05), C/C rs_7927894 FLG has a reverse association with a trend to significance (r=-0.194, p=0.07). Mean serum concentrations of TARC/CCL17 did not differ significantly among patients cohorts of the main and control groups, respectively: general main group — 615.8 pg/ml, main with a CP AD isolated — 651.3 pg/ml, main with a CP of AD combined with comorbid AtD — 585.4 pg/ml, control — 608.4 pg/ml (p>0.05). Associations of serum TARC/CCL17 concentrations were determined as follows: elevation trending to significance within increasing AD severity degree (r=0.290, p=0.07) and significant elevation within the AD exhacerbation period (r=0.426, p<0.05). No significant association of TARC/CCL17 as to AD patients compared to the control group was detected in our study (r=-0.027, p>0.05). Conclusions. The genotype heterozygote variant C/T rs_7927894 FLG is significantly the most common and associated with all AD CP in children — isolated and combined with comorbid AtD. Variant C/C rs_7927894 of FLG gene is significantly reversely associated with AD in children. Serum concentrations of TARC/CCL17 did not reveal any significant differences between the AD patients and nonEatopic ones. However, they significantly elevate within AD exacerbation phase and trending to significance within AD severity degree increase in children. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: atopic dermatitis, children, associations, polymorphism, filaggrin, thymus- and activation regulated chemokine.

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