Behrouz Gharesi-Fard; Maryam Zare; Eskandar Kamali-Sarvestani
Volume 14, Issue 4 , December 2017, , Pages 306-315
Abstract
Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, ...
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Background: Multiple Sclerosis (MS) with four different types is one of the well studied autoimmune diseases of the central nervous system. Generally, two-thirds of MS patients are females who are at risk of pregnancy-related complications. Inappropriate responses of mother’s immune system, such as antibody production against placental proteins, may lead to pregnancy-related disorders. The association between pregnancy complications and some autoantibodies including anti-phospholipid and anti-angiotensin II type-1 receptor antibodies are clear examples in this regard. Objective: To investigate the probable placental antigens that might be targeted by the antibodies in the sera of MS patients. Methods: Total placental proteins were extracted from normal fresh placentas and were separated using two-dimensional gel electrophoresis (2-DE) technique. The separated proteins were transferred onto a Polyvinylidene Fluoride (PVDF) membrane and blotted with the pooled sera of MS women or healthy controls (20 individuals in each group). The differentially blotted spot was identified by mass spectrometry and confirmed by western blot technique. Results: The results indicated that the women afflicted with MS had an antibody against placental HSP70kDa protein 5 (GRP78). Conclusion: In the present study, a new placental autoantigen candidate, which was targeted by antibody present in MS women sera, was found. The clinical importance of this finding regarding pregnancy complications in MS patients should be investigated by further experiments.
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.
Ladan Sadeghi; Eskandar Kamali-Sarvestani; Negar Azarpira; Mehrdad Shariati; Mohammad Hossein Karimi
Volume 11, Issue 3 , September 2014, , Pages 177-188
Abstract
Background: Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity. Objective: To evaluate the immunomodulatory ...
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Background: Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity. Objective: To evaluate the immunomodulatory effects of MSCs supernatant on maturation and function of DCs. Methods: Bone marrow derived mice MSCs were isolated and cultured. Twenty-four, forty-eight and seventy-two hours after passage 6, supernatants were collected and MSCs were assessed by cytometric analysis for the expression of CD34, CD44, CD45 and SCA-1. Splenic DCs were isolated using MACS and then co-cultured with MSCs supernatant. Expression of CD86, CD40 and MHC-II on DCs were also evaluated by cytometry. H 3-thymidine incorporation by proliferating T cells was determined in two separate MLR assay settings. In one setting, DCs were co-cultured with T cells in the presence of MSCs supernatant, and in the other setting DCs were treated with MSCs supernatant and then were co-cultured with T cells. Production of IL-12, IL-6 and IL-10 cytokines was measured in the supernatant of DCs treated with MSCs supernatant. We also measured IFN- γ and IL-4 levels in MLR supernatant. Results: The results showed that 72h MSCs supernatant could decrease the expression of MHC-II and CD86. The T cell proliferation was inhibited in the presence of MSCs supernatant and MSCs supernatant treated DCs as demonstrated by MLR assay. A significant increase in IL-4 level and a non significant decrease in IFN- γ level in MLR supernatant were observed. However, IL-6, IL-10 and IL-12 production did not change significantly. Conclusion: MSCs supernatant has a time dependent effect on the maturation of DCs. Also, it could alter cytokine production from responding T cells toward Th2. Generally, the findings of this study supported the immunomodulatory effect of MSCs supernatant on DCs maturation and function.
