Masumeh Darai; Saeede Soleimanian; Ramin Yaghobi; Kourosh Kazemi; Saman Nikeghbalian; Negar Azarpira
Abstract
Background: Cytomegalovirus (CMV) reinfection in transplant patients has been associated with graft loss and decreased patient survival. In this regard, the HLA-G molecule has the immunomodulatory characteristic and its soluble isoforms have important roles in immunity to viruses. The 14bp insertion/deletion ...
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Background: Cytomegalovirus (CMV) reinfection in transplant patients has been associated with graft loss and decreased patient survival. In this regard, the HLA-G molecule has the immunomodulatory characteristic and its soluble isoforms have important roles in immunity to viruses. The 14bp insertion/deletion polymorphism impacts HLA-G mRNA stability. Regarding the HLA-E molecule, two nonsynonymous alleles, HLA-E*0101, and HLA-E*0103 are different in their functions including the affinity of the relative peptide. Objective: To explore the possible link between HLA-G and HLA-E polymorphisms with CMV reinfection among liver transplant recipients (LTRs). Methods: In this study, a total of 140 liver transplantations were performed; of which 70 CMV-reactivated LTRs and 70 CMV non-reactivated ones were recruited. The cut-off value of CMV DNA was determined to be 100 copies/mL. PCR evaluated different genotypes for HLA-G and ARMS-PCR for HLA-E*0101 and *0103. Results: Neither the HLA-G genotypes (-14 bp/-14bp and +14bp/+14 bp homozygous genotypes with the p-values: 0.43, and 0.13, respectively +14 bp⁄-14 bp heterozygous genotype with p-value: 0.49) nor the HLA-E genotypes (HLA-E*0101/0103, HLA-E*0101/0101, and HLA-E*0103/0103 with the p-values: 0.152, 0.249, and 0.391, respectively) had any association with CMV reinfection in the LTRs. Conclusion: No difference was observed in the HLA-E and HLA-G genotype frequencies between our studied groups. Further studies are needed to explore other genetic variations and evaluate soluble HLA-G and HLA-E levels in the transplant population.
Afsoon Shariat; Mohammad Hossein Karimi; Talat Mokhtariazad; Seyed Mohammad Moazzeni; Bita Geramizadeh; Seyed Ali MalekHosseini; Ramin Yaghobi
Volume 11, Issue 3 , September 2014, , Pages 153-165
Abstract
Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant ...
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Background: Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. Objective: To compare the level of DC maturation and function in liver transplant recipients with healthy controls. Methods: In this study, twelve peripheral blood samples were selected from six liver transplant patients and six healthy controls. After the generation of DCs from monocytes, expression levels and mean fluorescent intensity (MFI) of several DC maturation markers were evaluated using flowcytometry. Secretion of IL-6, IL-12 and IL-23 proinflammatory cytokines was determined using ELISA. Gene expressions of TLR-2, TLR-4 and IL-23 were analyzed using real-time PCR. Results: DC expression markers including CD83 (p=0.007) and CD86 (p=0.02), as well as secretion of IL-6 (p=0.02) and IL-12 (p=0.007) by DCs were significantly increased in liver transplant patients compared with healthy controls. The MFI of CD86 (p=0.009) and HLA-DR (p= 0.005) expression on DCs was also higher in patients. The expression of TLR-2 transcripts in DCs of patients was higher than that of the controls (p=0.03). Conclusion: Based on these findings, increased frequency of DCs expressing CD83 and CD86, higher expression of CD86, HLA-DR, and TLR-2 as well as elevated secretion of proinflammatory cytokines in DCs of liver transplant recipient's point to the more mature phenotype and active function of DCs in patients compared with controls.
Afsoon Afshari; Ramin Yaghobi; Mohammad Hossein Karimi; Mojtaba Darbooie; Negar Azarpira
Volume 11, Issue 1 , March 2014, , Pages 29-39
Abstract
Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute ...
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Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute rejection. Methods: Ninety seven adult liver transplant patients who enrolled in this cross sectional study were divided into Non- Acute Rejected (Non-AR) and Acute Rejected (AR) patient groups. Three blood samples were collected from each patient in days 1, 4 and 7 post liver transplantation. The IL-17 mRNA levels were evaluated using an in-house real time PCR protocol. IL- 17 protein levels were also analyzed in Non-AR, AR and also control groups using ELISA method. Results: The IL-17 mRNA expression level continuously increased in AR patients in all days of follow-up post liver transplantation. IL-17 expression was, however, down regulated after day 4 post-transplant follow-up in Non-AR patients. Both IL-17 mRNA expression and protein levels were also significantly increased in AR patients compared with Non-AR ones. Conclusion: Based on these findings, significant increase of IL-17 mRNA and protein levels in AR patients highlights the important role of IL-17 in acute liver rejection.