Behrouz Gharesi-Fard; Fatemeh Mobasher-Nejad; Fatemeh Nasri
Volume 13, Issue 4 , December 2016, , Pages 296-308
Abstract
Background: Pre-eclampsia (PE) is known as a main factor contributing to
fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth
week of gestation. The balance of T helper subsets is essential to sustain a normal
pregnancy and preventing fetomaternal complications. Objective: ...
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Background: Pre-eclampsia (PE) is known as a main factor contributing to
fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth
week of gestation. The balance of T helper subsets is essential to sustain a normal
pregnancy and preventing fetomaternal complications. Objective: To investigate
differences in the levels of transcription factors and cytokine gene expression of
Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15
PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy.
Methods: Using Quantitative real-time PCR (Q-PCR), The expression of T-BET,
GATA-3, ROR-ɣt, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4,
IL-31, IL-17, IL-23, TGF-β1, TGF-β2, TGF-β3, and IL-35 in the placenta were
compared at mRNA levels between groups. Results: FOXP3 and GATA-3 were
significantly down-regulated, while T-BET was up-regulated in PE deciduae compared
to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the
chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE
placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides,
most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines
were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-ɣ/IL-35, IL-
6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio
was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy
controls. Conclusion: Our results shed more light on the contribution of
Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy.
Moreover, regulatory T cells and IL-35 seem to play a central role in the regulation of
all subsets.
Zeinab Tavakkol Afshari; Hamid Reza Rahimi; Seyed Morteza Ehteshamfar; Rashin Ganjali; Fatemeh Tara; Abbas Shapouri Moghadam
Volume 13, Issue 4 , December 2016, , Pages 309-316
Abstract
Background: Pre-eclampsia is the most common critical condition during pregnancy.
Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta
(IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant
women. Objective: To investigate the polymorphisms ...
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Background: Pre-eclampsia is the most common critical condition during pregnancy.
Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta
(IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant
women. Objective: To investigate the polymorphisms of IL-1β (C+3954T), TNF-α (G-
308A), and (G-238A) in preeclemptic women northeastern Iran. Methods: This study
was conducted on 153 preeclamptic women (case group) and 150 healthy pregnant
women (control group), admitted to Ghaem and Imam Reza hospitals of Mashhad, Iran.
IL-1β (C+3954T), TNF- α (G-238A) and TNF-α (G-308A) gene polymorphisms in the
promoter region were screened by polymerase chain reaction. Data were analyzed,
using SPSS version 16.0. Results: The mean age of the participants in the case and
control groups was 28.2 ± 6.1 and 27.1 ± 6.3 years, respectively (P=0.68). The
frequency of G-308A polymorphism was significantly higher in the case group,
compared to the control group (p<0.001). However, no significant relationship was
found between IL-1β genotype and pre-eclampsia (p=0.39). The frequency of TNF- α
(G-238A) AA genotype was significantly higher in the case group, while GG genotype
was less frequently detected in the case group, compared to the control group (p<0.001
for both genotypes). Moreover, the frequencies of AA genotypes of -238 TNF-α and G-
308A polymorphisms were significantly higher in the case group, compared to the
control group (p<0.001). Conclusion: The significant correlation between inflammation
promoting genotypes of TNF-α and Pre-eclampsia is noteworthy and provides evidence
on the contribution of immune related genes in this disease.
Fahimah Anvari; Feryal Dabagh-Gorjani; Mohammad-Sadegh SoltaniZangbar; Eskandar Kamali-Sarvestani; Zahra Malek-Hosseini; Behrouz Gharesi-Fard
Volume 12, Issue 2 , June 2015, , Pages 117-128
Abstract
Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral ...
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Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. Objectives: To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. Methods: A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. Results: Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. Conclusions: The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.
Leila Rezanezhad; Jaleh Zolghadri; Behrouz Gharesi-Fard
Volume 10, Issue 4 , December 2013, , Pages 238-246
Abstract
Background: Preeclampsia (PE) is a pregnancy specific syndrome that is associated with high maternal and fetal morbidity and mortality. Glucose regulated protein78 (GRP78) is an Endoplasmic Reticulum (ER) protein which is expressed on the cell surfaces of trophoblast cells under stress or hypoxic condition. ...
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Background: Preeclampsia (PE) is a pregnancy specific syndrome that is associated with high maternal and fetal morbidity and mortality. Glucose regulated protein78 (GRP78) is an Endoplasmic Reticulum (ER) protein which is expressed on the cell surfaces of trophoblast cells under stress or hypoxic condition. GRP78 has a role in aggressive behavior of invasive cells and may play a role in normal placentation. Objectives: To investigate the autoantibody against GRP78 in the sera of patients with PE and to assess the correlation between antibody and severity of the disease. Methods: We evaluated the anti-GRP78 antibody within the sera of fifty pre-eclamptic (12 severe and 38 mild PE) and fifty healthy pregnant women using a home-made ELISA assay. Furthermore, western blot technique was used to assess the expression of GRP78 in placenta of healthy and pre-eclamptic women in their third trimester. The presence of anti-GRP78 antibody in the serum samples from pre-eclamptic and healthy women was also assessed. Results: GRP78 was expressed by placenta, and both healthy and preeclamptic women produced anti-GRP78 antibody. Although no significant difference was found between the pre-eclamptic and healthy women regarding the level of anti-GRP78 antibody, the difference between severe pre-eclamptic and healthy control women was statistically significant (p<0.003). Conclusion: The findings of the present study indicated that measurement of anti-GRP78 antibody may provide a new marker for severe pre-eclampsia. Yet, future studies are required to confirm this notion.
Behrouz Gharesi-Fard; Leila Jafarzadeh; Jaleh Zolghadri; Hossein Haghbin
Volume 9, Issue 4 , December 2012, , Pages 234-240
Abstract
Background: Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. ...
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Background: Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. Objective: The aim of this study was determination of the sCD30 level in RPL and PE patients. Methods: The sCD30 level was measured in sera of a group of normal non-pregnant women (N=43) and compared with normal pregnancy at the first (N=42) and third (N=42) trimester. Furthermore, the level of sCD30 in the normal first and third trimester pregnancies were compared with that of RPL (N=38) and severe pre-eclamptic (N=41) patients, respectively. sCD30 levels were measured by ELISA method and student t-test was used for statistical analysis. Results: The mean level of sCD30 at the first trimester in normal pregnancy was significantly elevated as compared with normal non-pregnant women (21.4 vs. 15.2 ng/ml, p<0.0001). A significant difference between sCD30 concentration at the first and third trimester of normal pregnancies was also observed (21.4 vs. 14.3 ng/ml, p<0.0001). Interestingly, the sCD30 concentration did not show any significant changes at the first trimester of normal pregnancy as compared with RPL (21.4 vs. 20.9 ng/ml) and third trimester of normal pregnancy as compared with PE (14.3 vs. 13.1 ng/ml). Conclusion: The data of this study indicated that the concentration of sCD30 in serum during pregnancy period is not associated with RPL or PE and serum sCD30 is not a good correlate of Th2 immune responses in pregnancy.
