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.
Ghasem Solgi; Gholamreza Pourmand; Abdorasool Mehrsai; Mohsen Tahei-mahmoudi; Mohammad Hossein Nicknam; Mohammad Ebrahimi Rad; Ali Seraji; Amirabbas Asadpoor; Bita Ansaripor; Behrouz Nikbin; Aliakbar Amirzargar
Volume 7, Issue 1 , March 2010, , Pages 18-29
Abstract
Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion ...
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Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion (DBMI). Methods: Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA spe-cific panel for antibody specification. Results: Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Con-clusion: Our findings reveal an association between pre- and post-transplant anti-HLA an-tibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.
Ali Akbar Amirzargar; Morteza Bagheri; Ardeshir Ghavamzadeh; Kamran Alimoghadam; Farideh Khosravi; Mohammad Hossein Nicknam; Mandana Moheydin; Bita Ansaripour; Batul Moradi; Behrouz Nikbin
Volume 1, Issue 1 , June 2004, , Pages 26-33
Abstract
Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion ...
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Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion of cytokines is dependent, at least in part, on genetic polymorphism (nucleotide variations) within the promoter region or other regulatory sequences of cytokine genes. The majority of polymorphisms described are single nucleotide polymorphism (SNPs). The objective of this study was to analyze the genetic profile of Th1 and Th2 cytokines in 30 Iranian patients with CML and 40 healthy subjects. Methods: In the patients and control subjects, the allelic and genotype frequencies were determined for the cytokine genes. All typing were performed by PCR-SSP assay. Allele and genotype frequencies were calculated and compared with those of normal controls. Results: The results showed that the most frequent alleles in our patients were TGF-b TG/TG, IL-4 T at position -1089, C at position -590, T at position -33 and IL-10 A at position -1082. Whereas the following alleles - TGF-b CG/CG and IL-10 C at position -592 – were seen in much lower frequencies. Conclusion: In conclusion, it could be suggested that the frequency of high producing TGF-b alleles and low producing IL-4 and IL-10 alleles in the CML patients is higher than the normal subjects.