Başkent Üniversitesi Yayınları
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Item CTLA4 CT60 A/G Gene Polymorphism in Liver Transplant Recipients(Başkent Üniversitesi, 2010-09) Azarpira, Negar; Daraie, Masumeh; Aghdaie, Mahdokht Hosein; Malekhosseini, Seyed AliObjectives: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and the single nucleotide polymorphism A/G in the CTLA-4 CT60 gene in liver transplant recipients. Materials and Methods: Fifty-one liver transplant recipients with at least 3 months’ follow-up were selected and genotyped for CTLA-4 CT60 polymorphism (HpyCH4 IV). The association of each genotype with allograft acute rejection was evaluated. Results: The mean age of patients was 27.9 ± 15.17 years (minimum, 1 year, maximum, 55 years), with 39% male and 61% female. Overall, 17 recipients (33.3%) experienced acute rejection within the first 3 months after a liver transplant. In our study, 50% of the patients (n=26) have G/A , 31% (n=16) have A/A, and 17% have G/G genotypes (n=9). Distribution of alleles was not different according to underlying liver disease. There also was no difference in sex, age, and distributions of CTLA-4 CT60 alleles with acute rejection episodes. Conclusions: CT60 A/G dimorphism within the 3'-UTR of CTLA4 gene does not influence acute rejection development in liver transplant. However, organ rejection is determined by a combination of several genetic traits rather than a single gene. Therefore, more studies with larger patient numbers are necessary to investigate the effect of combinations of genetic phenotypes involved in this process.Item Liver Transplant: A Primer(Başkent Üniversitesi, 2010-06) Movahedi, Zohreh; Saab, Sammy; Holt, Curtis D.Liver transplant has been accepted as a successful therapeutic option for patients with end-stage liver disease. Patient and graft survival has incrementally increased over the past 2 decades, mainly because of immunosuppressive regimens. However, the nonspecific nature of immunosuppressive agents is associated with an increased risk of development of opportunistic infections, renal impairment, metabolic derangements, neurotoxicity, de novo malignancies, and recurrence of the primary disease. Immunosuppressive regimen pharmacologic classes include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids, and antibody-based therapies. These agents affect T-cell–dependent B-cell activation, and target different sites in the T-cell activation cascade by inhibiting T-cell activation or causing T-cell depletion. The goals of immunosuppression in solid-organ transplant are to prevent allograft rejection as well as optimize allograft function, prolong patient survival, and improve patient quality of life. Therefore, it is essential to carefully select the immunosuppressive regimen that will result in significant improvements in long-term liver transplant patients’ survival and quality of life.Item Value of Donor-specific Antibody Detection in First-Graft Renal Transplant Recipients with a Negative Complement-dependent Cytotoxic Crossmatch(Başkent Üniversitesi, 2009-06) Kamal, Mohamed Mohamed; Ghoneim, Mohamed Ahmed; Mahmoud, Khaled Mohamed; Ismail, Amani Mostafa; Sheashaa, Hussein Attia; Gheith, Osama AshryObjectives: The clinical significance of pretransplant donor specific antihuman leukocyte antigen antibodies that occur despite negative cytotoxicity crossmatches is still unclear. In this study, we assessed the impact of those antibodies on the outcome of renal transplants. Materials and Methods: Our study subjects consisted of 153 living-donor kidney transplant recipients whose pretransplant sera were available. All subjects had a negative complement-dependent cytotoxic crossmatch and were retrospectively evaluated for antihuman leukocyte antigen antibodies and their donor specificities by means of LABScan 100 Flow analyzer (Luminex Corporation, Texas, USA). The follow-up data of all subjects were reviewed. Results: Antihuman leukocyte antigen antibodies were detected in 49 patients, donor nonspecific antihuman leukocyte antigen antibodies were found in 33, and donor specific antihuman leukocyte antigen antibodies were identified in 16. There was a trend toward more acute rejection in the patients with antihuman leukocyte antigen antibodies (22%) than in those without antihuman leukocyte antigen antibodies (17%), but that difference had no statistical significance (P = .378). Patients with donor specific antihuman leukocyte antigen antibodies had a significantly higher incidence of acute cellular rejection (19% vs. 6%, respectively) and vascular rejection (25% vs. 6%, respectively) than did patients with donor nonspecific antihuman leukocyte antigen antibodies (P = .04). Conclusions: Our results suggest that there is a higher incidence of acute rejection in patients with donor specific antihuman leukocyte antigen antibodies and a negative complement-dependent cytotoxic crossmatch; however, those factors had no statistically significant impact on patient or graft survival.Item Early Diagnosis and Successful Treatment of Acute Antibody-Mediated Rejection of a Renal Transplant(Başkent Üniversitesi, 2008-09) Yang, Ya-Wen; Tsai, Meng-Kun; Lee, Po-Huang; Wu, Ming-Shiou; Lin, Wei-ChouAntibody-mediated rejection is a delicate situation. It rarely occurs but when it does, it usually results in graft dysfunction and frequently, graft loss. There has been no standard protocol for treating antibody-mediated rejection, although several therapeutic protocols have been recommended. Early detection and treatments of suspected antibody-mediated rejection can secure the graft and improve its function. Here, we describe a typical case of antibody-mediated rejection in a 46-year-old woman who was successfully treated with intravenous immunoglobulin, plasmapheresis, and the anti-CD20 monoclonal antibody, rituximab.Item Influence of Long Chain Polyunsaturated Fatty Acids and Ornithine Concentrations on Complications After Renal Transplant(Başkent Üniversitesi, 2008-06) Alexander, J. Wesley; Woodle, E. Steve; James, J. Howard; Moser, Ann B.; Kuo, Paul C.; Light, Jimmy A.; Succop, Paul; Goodman, Hope R.Objectives: The present study, registered at clinicaltrials.gov with the unique registration number NCT00560014, sought to evaluate the relations between fatty acid concentrations in red blood cells or plasma and amino acid concentrations in plasma on rejection, calcineurin inhibitor toxicity, and new-onset diabetes mellitus. Materials and Methods: Lipid profiles on plasma or red blood cell samples were performed preoperatively and postoperatively in 54 patients. Plasma amino acid profiles were obtained in 49 of these patients. Results: High concentrations of total ω-3 fatty acids, eicosapentaenoic and docosahexaenoic acids in red blood cells, and ornithine in plasma, all were associated with a significantly lower incidence of rejection, whereas high total ω-6 fatty acids were associated with a high rejection rate. Calcineurin inhibitor toxicity was associated with low levels of docosahexaenoic acid, ornithine, and the ω-3 index, and high total ω-6 and ω-3/ω-6 ratios. Inhibition of new-onset diabetes mellitus was seen only with high levels of ornithine. Peak concentrations of fatty acids in red blood cells were not obtained until after 30 days. High levels of arginine were not associated with reduced complications. Conclusions: The levels of selected nutrients in plasma and red blood cell membranes appear to have a profound effect on complications after renal transplant. These preliminary results need confirmation in prospective randomized clinical trials.Item Cytokine Gene Polymorphisms in Renal Transplant Recipients(Başkent Üniversitesi, 2006-12) Azarpira, N.; Aghdaie, MH.; Geramizadeh, B.; Behzadi, S.; Nikeghbalian, S.; Sagheb, F.; Rahsaz, M.; Behzad-Behbahanie, A.; Ayatollahi, M.; Darai, M.; Azarpira, MR.; Banihashemie, M.; Tabei, SZ.Objective: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial. Materials and Methods: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-α) (-308 G/A), and interferon-gamma (IFN-γ) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria. Results: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL-10, TNF-α genes, or dinucleotide repeat polymorphisms in the IFN-γ gene. Conclusions: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.