scholarly journals Changes in the expression of HLA-DR on lymphocyte subpopulations of spouses having children with sporadic congenital heart defects without chromosomal diseases, under the influence of female’s autoserum

2021 ◽  
Vol 23 (1) ◽  
pp. 143-148
Author(s):  
A. V. Shabaldin ◽  
S. V. Grivtsova ◽  
N. S. Deeva ◽  
S. A. Shmulevich ◽  
A. V. Tsepokina ◽  
...  
Keyword(s):  
Immune Response ◽  
Mixed Culture ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Married Couples ◽  
Control Group ◽  
Study Group ◽  
Hla Dr ◽  
Chromosomal Diseases

This study is aimed to investigate the effect of female autoserum on the HLA-DR expression in various subpopulations of lymphocytes obtained from spouses with children with sporadic congenital heart defects without chromosomal diseases. 78 married couples with children with congenital heart disease were included in the study group. The control group was formed from 35 married couples with healthy children. The immune response in a mixed culture of lymphocytes of spouses was evaluated by an increased HLA-DR expression in a mixed culture in relation to spontaneous cultures of lymphocytes. Primary staining of female and male lymphocytes by monoclonal antibodies to CD45 conjugated with various fluorescent dyes (PC-5 and PC-7) was performed to assess the immune response of female lymphocytes to male ones and vice versa. The activating effect of female autoserum on all subpopulations of female lymphocytes simultaneously occurred significantly less frequently in the study group compared to the control. The control group was characterized by the domination of the positive effect of female autoserum on HLA-DR expression for all subpopulations of female lymphocyte. For all female lymphocytes having HLA-DR molecule on its membrane, the blocking effect of female autoserum in the study group was significantly more expressed in relation to the control group. Thus, the effect of female autoserum is manifested in relation to the HLA-DR expression on its own lymphocytes, but not on the lymphocytes of the spouse.

scholarly journals PECULIARITIES OF ALLOGENIC INTERACTIONS IN THE SHORT-TERM CULTURE OF LYMPHOCYTES OF SPOUSES WHO HAVE CHILDREN WITH CONGENITAL HEART DISEASES OR EARLY REPRODUCTIVE LOSSES

2019 ◽  
Vol 21 (2) ◽  
pp. 279-292 ◽  
Author(s):  
A. V. Shabaldin ◽  
S. A. Shmulevich ◽  
G. N. Chistyakova ◽  
I. I. Remizova ◽  
E. B. Lukoyanycheva ◽  
...  
Keyword(s):  
Immune Response ◽  
Mixed Culture ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Married Couples ◽  
Healthy Children ◽  
Short Term ◽  
Reproductive Losses ◽  
Short Term Culture

We have studied HLA allogeneic interactions in short-term cultures of lymphocytes from the parents having children with congenital heart defects (CHD), or subject to early reproductive losses. Twentyone married couples (CHD as the main group) who had children with sporadic CHD (interventricular septal defect) without chromosomal diseases were observed. Fifty married couples (a comparison group) had two or more reproductive losses in early gestation (up to 9 weeks), denoted as PNPs (miscarriages, missed abortions, habitual miscarriages. Forty-one families with three or more healthy children represented a control group. Immune response in cell cultures was evaluated by increasing expression of HLA-DR in a mixed culture, as compared to spontaneous lymphocyte cultures. Initial labeling of female and male lymphocytes with monoclonal antibodies to CD45 conjugated to different fluorescent dyes (PC-5 and PC-7) allowed us to evaluate the immune response of female lymphocytes to males and vice versa. The suppressor effect of autologous female serum upon the mixed culture of the lymphocytes of the spouses was also evaluated. Results of the present study showed a difference in HLA allogeneic interactions in the short-term culture of lymphocytes registered for spouses with reproductive losses and children with congenital heart defects. Reproductive losses were associated with a low blocking effect of female auto-serum upon allogeneic HLA interactions in the short-term culture of the lymphocytes of the spouses. Congenital heart defects were associated with high activity of female B-lymphocytes (CD3-/HL-DR+) in short-term mixed culture of lymphocytes from the spouses.

scholarly journals The role of maternal HLA-DR and HLA-G loci in determining the risk of sporadic congenital heart defects in the next generation

2021 ◽  
Vol 66 (5) ◽  
pp. 42-48
Author(s):  
N. S. Deeva ◽  
A. V. Tsepokina ◽  
S. A. Shmulevich ◽  
A. V. Shabaldin
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Human Leukocyte ◽  
Next Generation ◽  
Chain Reaction ◽  
Hla Dr ◽  
Polymerase Chain ◽  
Chromosomal Diseases

The paper considers the role of maternal HLA-DR (Human Leukocyte Antigens-DR) and HLA-G (Human Leukocyte Antigen-G) loci in determining the risk of the formation of sporadic congenital heart defects without chromosomal diseases in the next generation. The HLA-G molecule expressed on trophoblast performs a protective function by blocking killer receptors on natural killer cells (NK cells). At the same time, the maternal alleles of HLA-DRB1 restrict the immune response to allogeneic antigens of the paternal embryo, which may affect the severity of inflammation in the mother-embryo system and through this mechanism induce the formation of heart disease.Objective: to study the frequency distribution of the combinations of alleles and genotypes of HLA-G 3’UTR and HLA-DRB1 in women with children with sporadic congenital heart defects without chromosomal diseases. Children characteristics and research methods. There were formed 2 groups: Main Group (103 women with children with sporadic congenital heart defects without chromosomal diseases) and Control Group (103 women with conditionally healthy children). Genomic DNA was isolated by phenol-chloroform extraction. Typing of HLA-G 3’UTR 14-bp insertion/deletion was performed by amplification of polymorphic regions of genes by polymerase chain reaction with further electrophoretic detection in polyacrylamide gel 6.0. The frequency analysis of 14 alleles of the HLA-DRB1 gene was performed by real-time polymerase chain reaction. In the course of this work the authors identified predictor and protective combined genotypes.Conclusion. HLA-DRB1 and HLA-G 3’UTR 14-bp ins/del (rs 1704) make a significant contribution to determining the risk of the formation of sporadic congenital heart defects without chromosomal diseases in the next generation.

scholarly journals Retrospective analysis of prenatal echcardiography findings in cases of congenital heart defects: comparison with postnatal pulmonary hypertension revealed by lungs histopathology (2010-2015)

2015 ◽  
Vol 5 (4) ◽  
pp. 12-18
Author(s):  
Hanna Romanowicz ◽  
Ewa Czichos ◽  
Katarzyna Zych-Krekora ◽  
Michał Krekora ◽  
Maciej Słodki ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Retrospective Analysis ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Neonatal Outcome ◽  
Heart Defects ◽  
Control Group ◽  
Study Group ◽  
Neonatal Deaths

Abstract Introduction: It was retrospective analysis of prenatal echocardiography findings in fetuses with congenital heart defects, who died in our institution and had an autopsy exams in years 2010 - 2015. Material and methods: Among total 115 deaths the pulmonary hypertension based on histopathology criteria was present in 83 cases (72%) as a leading cause of their deaths. Out of 83 neonates 40 underwent prenatal echo, 43 did not, however in both groups there were similar types of heart defects. Results: The prenatal echo findings from study group (n=40), from the last echo before the delivery were compared with control group and group of HLHS who did survive neonatal surgery and were discharged from hospital. There were statistical differences between pulmonary artery/aorta ratio in fetuses in control group and fetuses in study group („pulmonary hypertension” after birth) (p=0,044). There were statistical differences between pre-delivery pulmonary artery/aorta ratio in fetuses in study group (with „pulmonary hypertension” after birth) and in group of fetuses with HLHS, alive & well after first surgery (p=0,027). There were no differences between pulmonary artery/ aorta ratio fetuses in control group and fetuses with HLHS, alive & well after first surgery (p=0,38) Conclusion: 1) Pulmonary hypertension was a frequent cause of neonatal deaths among our series of congenital heart defects 2) Dilatation of pulmonary artery (and increased pulmonary/artery ratio ) in fetal echo just before delivery may be an important risk factor for poor neonatal outcome in congenital heart defects.)

scholarly journals Congenital Heart Defects Are Rarely Caused by Mutations in Cardiac and Smooth Muscle Actin Genes

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Tatiana Khodyuchenko ◽  
Anna Zlotina ◽  
Tatiana Pervunina ◽  
Dmitry Zverev ◽  
Anna Malashicheva ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Smooth Muscle Actin ◽  
Ductus Arteriosus ◽  
Control Group ◽  
Missense Mutations ◽  
Muscle Actin ◽  
Cardiac Actin

Background. Congenital heart defects (CHDs) often have genetic background due to missense mutations in cardiomyocyte-specific genes. For example, cardiac actin was shown to be involved in pathogenesis of cardiac septum defects and smooth muscle actin in pathogenesis of aortic aneurysm in combination with patent ductus arteriosus (PDA). In the present study, we further searched for mutations in humanα-cardiac actin (ACTC1) and smooth muscleα-actin (ACTA2) genes as a possible cause of atrial septum defect type II (ASDII) and PDA.Findings. Total genomic DNA was extracted from peripheral blood of 86 individuals with ASDs and 100 individuals with PDA. Coding exons and flanking intron regions ofACTC1(NM_005159.4) andACTA2(NM_001613) were amplified by PCR with specific primers designed according to the corresponding gene reference sequences. PCR fragments were directly sequenced and analyzed. Sequence analysis ofACTC1andACTA2did not identify any nucleotide changes that altered the coding sense of the genes. InACTC1gene, we were able to detect one previously described nucleotide polymorphism (rs2307493) resulting in a synonymous substitution. The frequency of this SNP was similar in the study and control group, thus excluding it from the possible disease-associated variants.Conclusions. Our results confirmed that the mutations inACTC1gene are rare (at least <1%) cause of ASDII. Mutations inACTA2gene were not detected in patients with PDA, thus being excluded from the list of frequent PDA-associated genetic defects.

scholarly journals Combination of HLA-DRB1 alleles as a factor causing risks of sporadic congenital heart defects and congenital malformations without chromosome diseases

2021 ◽  
pp. 133-142
Author(s):  
A.V. Shabaldin ◽  
◽  
A.V. Tsepokina ◽  
O.V. Dolgikh ◽  
E.V. Shabaldina ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Malformations ◽  
Congenital Heart ◽  
Heart Defects ◽  
Married Couples ◽  
Specific Weight ◽  
Healthy Children ◽  
Early Diagnostics ◽  
Genetic Predictors ◽  
Research Goal

Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes. Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies. We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research. Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children. Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

scholarly journals Prevalence of Growth Restriction at Birth for Newborns With Congenital Heart Defects: A Population-Based Prospective Cohort Study EPICARD

2021 ◽  
Vol 9 ◽  
Author(s):  
Ali Ghanchi ◽  
Makan Rahshenas ◽  
Damien Bonnet ◽  
Neil Derridj ◽  
Nathalie LeLong ◽  
...  
Keyword(s):  
General Population ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Population Based ◽  
Growth Restriction ◽  
Control Group ◽  
Using Data ◽  
Underlying Mechanisms ◽  
Adult Morbidity

Background and Objectives: Congenital heart defects (CHD) and growth restriction at birth are two major causes of childhood and adult morbidity and mortality. The aim of this study was to assess the overall risk of growth restriction at birth, as measured by its imperfect proxy small (&lt; 10th percentile) for gestational age (SGA), for newborns with CHD.Methods: Using data from a population-based cohort of children born with CHD, we assessed the risk of growth restriction at birth using SGA and severe SGA (3rd percentile). To compare the odds of SGA and severe SGA across five specific major CHD, we used ordinal logistic regression using isolated, minor (non-operated) ventricular septal defect (VSD) as the control group.Results: The overall proportion of SGA for “isolated” CHD (i.e., those not associated with other anomalies) was 13% (95% CI, 12–15%), which is 30% higher than what would be expected in the general population (i.e., 10%). The risk of severe SGA was 5% (95% CI, 4–6%) as compared with the expected 3% in the general population. There were substantial differences in the risk of overall SGA and more so severe SGA across the different CHD. The highest risk of SGA occurred for Tetralogy of Fallot (adjusted OR 2.7, 95% CI, 1.3–5.8) and operated VSD (adjusted OR 2.1, 95% CI, 1.1–3.8) as compared with the control group of minor (non-operated) VSD.Conclusion: The overall risks of both SGA and severe SGA were higher in isolated CHD than what would be expected in the general population with substantial differences across the subtypes of CHD. These results may provide a clue for understanding the underlying mechanisms of the relation between alterations in fetal circulation associated with different types of CHD and their effects on fetal growth.

scholarly journals Combination of HLA-DRB1 alleles as a factor causing risks of sporadic congenital heart defects and congenital malformations without chromosome diseases

2021 ◽  
pp. 133-142
Author(s):  
A.V. Shabaldin ◽  
◽  
A.V. Tsepokina ◽  
O.V. Dolgikh ◽  
E.V. Shabaldina ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Malformations ◽  
Congenital Heart ◽  
Heart Defects ◽  
Married Couples ◽  
Specific Weight ◽  
Healthy Children ◽  
Early Diagnostics ◽  
Genetic Predictors ◽  
Research Goal

Congenital heart defects are anomalies that are becoming more and more frequent every year. Their specific weight is the highest among all the defects and malformations in fetus. Besides, children with sporadic congenital heart defects and malformations are still born rather frequently. We made an assumption that congenital heart defects (CHD) and congenital malformations (CM) were formed due to inflammatory process decompensation within «mother – fetus» system occurring in case of a conflict as per HLA between a semi-allogenic fetus and its mother’s microenvironment. A risk of such a conflict might be associated with certain HLA combinations in parents’ genotypes. Our research goal was to reveal peculiarities of HLA-DRB1 alleles combinations in married couples who had children with sporadic CHD and CM without any chromosome diseases and to determine whether such peculiarities could cause risks of congenital anomalies. We determined frequency of 14 alleles in HLA-DRB1 gene in all people who took part in the research. Our research allowed establishing that parents whose children suffered from CHD more frequently had common HLA-DRB104, female HLA-DRB107 with male HLA-DRB113, HLA-DRB117 and female HLA-DRB113 with male HLA-DRB114. Children who suffered from CM more frequently had parents who were homologous as per HLA-DRB112, as well as with female HLA-DRB112 and male HLA-DRB101, HLA-DRB104, HLA-DRB113, and HLA-DRB115; this greater frequency was statistically significant. We also detected an authentic increase in frequency of HLA-DRB112 allele in children against their parents. Children with CM also had HLA-DRB112 allele statistically significantly more frequently than healthy children. Peculiarities related to HLA-DRB1 alleles combination are genetic predictors of CHD and CM occurrence; their determination will allow minimizing risks of such disorders due to early diagnostics and timely prevention.

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