Nahid Daraei; Mehri Ghafourian; Ata Ghadiri; Afshin Amari; Mahin Najafian; Saber Rokhafrooz
Abstract
Background: The development of a maternal immune response to fetal antigens and deficiency in regulatory T-cells (Tregs) may lead to preeclampsia. A plausible explanation for the reduced Treg cell function in women with preeclampsia is the presence of exhausted Treg cells which express CD279 or programmed ...
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Background: The development of a maternal immune response to fetal antigens and deficiency in regulatory T-cells (Tregs) may lead to preeclampsia. A plausible explanation for the reduced Treg cell function in women with preeclampsia is the presence of exhausted Treg cells which express CD279 or programmed cell death receptor-1 (PD-1), a negative regulatory molecule associated with limited proliferative capacity and reduced immune suppression. Objective: To assess the number of Treg CD4+ CD25high and exhausted Treg CD4+ CD25high CD279+ cells in women with preeclampsia (PE group) and healthy pregnant women (HP group) during the third trimester of pregnancy. Methods: Three-color flow cytometry was used to determine the proportion of Treg and exhausted Treg cells in 40 women in the PE group and 37 women in the HP group. Participants’ blood samples were placed in EDTA blood collection tubes. Peripheral mononuclear cells were separated from the samples and stained with flurochrome-conjugated antibodies against human CD4, CD25 and CD279 markers, and subsequently analyzed by flow cytometry. Results: The PE group had fewer Tregs compared to the HP group (p=0.011). There was a significant increase in the percentage of exhausted PD-1+(CD279) Tregs (p=0.035) in the PE group comparisons with the HP group. Conclusion: The increased number of PD-1 (CD279) molecules on the Treg cells may play a role in preeclampsia, hence it recommendation as a therapeutic target for the disease.
Tahereh Poordast; Fateme Sadat Najib; Rasoul Baharlou; Atena Bijani; Shaghayegh Moradi Alamdarloo; Alieh Poordast
Volume 14, Issue 2 , June 2017, , Pages 172-179
Abstract
Background: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology ...
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Background: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia. Objectives: To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia. Methods: Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-23 and TGF-β were measured by the enzyme linked immunosorbent assay (ELISA). Results: The serum levels of IL-17 and TGF-β were significantly higher in preeclampsia patients compared to normal pregnant group and healthy individuals (p>0.0001) but interestingly, the opposite was the case for IL-23 (p=0.005). However, there were no significant differences in IL-21 between preeclampsia and normal pregnant group. Conclusions: Our results conclude that contrary to IL-21, serum levels of IL-17 and TGF-β significantly increased in preeclampsia compared to normal pregnant women, supporting an imbalance of cytokine profile in preeclamtic patients.
Feryal Dabagh-Gorjani; Fahimeh Anvari; Jaleh Zolghadri; Eskandar KamaliSarvestani; Behrouz Gharesi-Fard
Volume 11, Issue 4 , December 2014, , Pages 233-245
Abstract
Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. ...
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Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. Objective: To investigate the differences in the expression of TLRs 2, 4, 5, and 6 and a group of inflammatory cytokines including IL-1, IL-6, TNF-α and IFN-γ in placentas from PE and healthy pregnant women in their third trimester of pregnancy. Methods: This case-control study was performed on fifteen PE and fifteen age and gestational matched healthy pregnant women in the third trimester of pregnancy. Real time PCR (RT-PCR) technique was used to determine the expression of TLRs 2, 4, 5, and 6 in the maternal and fetal parts of the placenta. Moreover, the expressions of IL-1, IL-6, TNF-α and IFN-γ at RNA level in placental samples, peripheral, and cord blood were investigated. Results: The results of the present study indicated that the expressions of TLRs 4, 5 and 6 were significantly increased in both maternal part (p<0.001 and p<0.003 for TLRs 4, 6 and TLR 5, respectively) and fetal part (p<0.001), while TLR2 showed significant increase only in the fetal part of PE placentas (p<0.002). The levels of all studied cytokines showed over-expression within peripheral and cord blood samples from PE patients (p<0.001 for IL-1, IL-6, and IFN-γ and p<0.004 for TNF-α in both cord and peripheral blood samples). Conclusion: The finding of the present study indicated that the expression of the studied TLRs and inflammatory cytokines are generally suppressed in normal pregnancy, but are up regulated in preeclamptic women. Moreover, it seems that the maternal and fetal parts of the placenta may play different roles in the induction of the inflammatory status within the placenta.
Reza Mansouri; Firoozeh Akbari; Mohammad Vodjgani; Fereidoun Mahboudi; Fathollah Kalantar; Mahroo Mirahmadian
Volume 4, Issue 3 , December 2007, , Pages 179-185
Abstract
Background: Preeclampsia is a major cause of mortality and morbidity and is also a leading cause of preterm birth and intrauterine growth retardation. Several studies have reported abnormal levels of cytokines in women with preeclampsia. Objectives: To detect serum levels of various cytokines in pregnant ...
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Background: Preeclampsia is a major cause of mortality and morbidity and is also a leading cause of preterm birth and intrauterine growth retardation. Several studies have reported abnormal levels of cytokines in women with preeclampsia. Objectives: To detect serum levels of various cytokines in pregnant women with and without preeclampsia in the third trimester of pregnancy. Methods: Thirty patients with preeclampsia and thirty normal pregnant women were enrolled in the study. Blood samples were taken and serum levels of IFN γ, IL-12p70, IL-18, IL-15, IL-4 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). Results: Preeclamptic women had significantly increased levels of circulating IL-12p70 (p < 0.05), IL-18 (p < 0.001), IL-4 (p < 0.001), IL-15 (p < 0.05) and IFN γ (p < 0.001). By contrast, circulating levels of IL-10 were not significantly different between the two groups. Conclusions: The present study supports the hypothesis of altered immune response in preeclampsia and suggests that dysregulation of cytokine expression occurs in preeclampsia with increased levels of IFN γ, IL-12p70, IL-15, IL-18 and IL-4.
Maryam Ayatollahi; Alamtaj Samsami Dehaghani; Ziaedin Tabei
Volume 2, Issue 1 , March 2005, , Pages 50-55
Abstract
Background: Successful pregnancy in allopregnant women depends upon the control of graft rejection mechanisms. It has been suggested that some immunosuppressive cytokines contribute to successful pregnancy and transplantation. Transforming growth factor beta (TGF- β) exhibits potent immunoregulatory ...
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Background: Successful pregnancy in allopregnant women depends upon the control of graft rejection mechanisms. It has been suggested that some immunosuppressive cytokines contribute to successful pregnancy and transplantation. Transforming growth factor beta (TGF- β) exhibits potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. Recent studies suggest a role for TGF- β in the generation of T-regulatory lymphocytes which preserves the tolerance to peripheral self antigens and may control the response to allogenic tissues and thereby promote the transplantation tolerance. Also, the function of TGF- β in trophoblast differentiation and hypertension is reported. Objective: To evaluate the maternal serum TGF- β1 level in normal allopregnant women and in pregnancies complicated by preeclampcia (PE). Methods: Sixty one pregnant preeclamptic women (32 cases with severe and 29 with mild PE), 22 normotensive healthy pregnant, and 20 non-pregnant controls constituted the studied groups. The active form of TGF- β1 in serum from all cases was investigated by indirect ELISA technique. Results: The results showed that TGF- β1 level was higher in all three pregnant groups as compared with the nonpregnant controls. No significant changes in serum levels of TGF- β1 were found in PE as compared with the normal pregnancy. Conclusion: TGF-β1 may function as a regulatory factor in fetal allograft survival during pregnancy, and TGF- β1 does not have a pathophysiological role in PE.