Yaghoub Mollaei-Kandelous; Pedram Ahmadpoor; Mohsen Nafar; Mohammad Reza Khatami; Samad Farashi Bonab; Nader Tajik; Mahdi Shekarabi; Aliakbar Amirzargar
Abstract
Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: ...
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Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.Objective: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.Methods: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.Results: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.Conclusions: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.
Morteza Hosseinzadeh; Mohsen Nafar; Pedram Ahmadpoor; Farshid Noorbakhsh; Mir Saeed Yekaninejad; Mohammad Hossein Niknam; Aliakbar Amirzargar
Volume 14, Issue 1 , March 2017, , Pages 24-34
Abstract
Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells ...
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Background: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. Objective: To investigate whether the expression of TLRs in peripheral blood mononuclear cells (PBMCs) can predict the clinical outcome of kidney allografts. Methods: We obtained blood samples from 52 renal transplant patients before transplant, and 2, 90, and 180 days post-transplantation in order to analyze the surface expressions of TLR-2 and TLR-4 on peripheral blood monocytes. The expression patterns of TLR-2 and TLR-4 were compared between patients with graft dysfunction (GD) and those with well-functioning graft (WFG). Results: Significantly different mean dynamic changes in surface expression of TLR-2, according to percentage of TLR-2+ cells, between (the GD and WFG) groups existed at most time-points before and after renal transplantation (p=0.007) with the exception of day 2 post-transplantation. We observed significantly higher mean fluorescence intensities of TLR-2 and TLR-4 on CD14+ cells in the GD group compared to the WFG group. This finding was particularly observed 180 days post-transplantation (p=0.001). Based on TLR-2 and TLR-4 protein expression for each step, multiple logistic regression and ROC curve analysis revealed that an increase in CD14+ TLR-2+ monocytes within the 90 days post-transplantaton was associated with increased risk of GD at 180 and 365 days post-transplantation [odds ratio (OR)=1.27, p=0.005)]. Conclusion: Sequential monitoring of TLR-2 and TLR-4 expression patterns in peripheral blood monocytes appear to be prognostic and predictive biomarkers for early and late kidney allograft outcomes.
Sara Assadiasl; Pedram Ahmadpoor; Mohsen Nafar; Mahboob Lessan Pezeshki; Fateme Pourrezagholi; Mahmoud Parvin; Abtin Shahlaee; Adel Sepanjnia; Mohammad Hossein Nicknam; Aliakbar Amirzargar
Volume 11, Issue 3 , September 2014, , Pages 139-152
Abstract
Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic ...
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Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- β1 in renal allografts. Methods: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF- β1 gene expression was assessed by Real Time PCR. Results: The percentage of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p<0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF- β1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers. Conclusion: The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF- β1, it is likely to be implicated in chronic damages of allograft tissue.
