الفهرس 
Patients and methodsOnly 14 pages are availabe for public view
 |  | from | 133 |  |  |
| | | from | 133 | | |
Abstract
T cell-mediated immune response has a critical role in kidney transplantation rejection mainly by recognizing allo-antigens and, therefore, in the immune response against the donor tissue. T cell needs two steps to be activated, the first which is antigen specific and needs TCR to bind peptide molecules attached to MHC on APC while the second occurs by the interaction of TCR with their specific ligands on the APC cell surface (costimulatory pathways). Costimulatory pathway occurs through CD28 on naiive T cell binding to B7 molecule on APCs either B7-1 (CD 80) or B7-2 (CD 86) , and this pathway is competitively inhibited by cytotoxic T-lymphocyte associated protein 4 (CTLA-4) binding also to B7 molecule and so negatively regulates T cell-mediated immune responses and induces immune tolerance. CTLA-4 moves to the cell surface of activated T cells with higher affinity for binding to B7 molecule on APCs than does CD 28 resulting in T-cell inactivation by delivering negative signals that inhibit cytokine release and down-regulate T cell proliferation. We aimed to investigate the association between CD 28 gene IVS3 +17T/C (rs3116496) polymorphism, CD86 gene +1057G/A (rs1129055) polymorphism, CTLA-4 gene +6230 A/G (rs3087243) polymorphism and PD-1.3 +7146 G > A (rs2227982) on acute renal allograft rejection and graft survival among Egyptian kidney transplant recipients. To achieve this aim, we conducted this non-concurrent cohort study of 269 consecutive kidney transplant recipients who underwent a living –donor kidney transplantation at our center in a period between January, 2014 and July, 2018. Of these, 32 patients were excluded from the study because of not fulfilling the inclusion criteria. Of the remaining 237 patients, 59 consecutive patients experienced histologically proven AR, nine patients were not available for follow up and the remaining 50 patients were enrolled in the study and were considered as the study group. Another 50 kidney transplant recipients who didn`t experience AR during the same period were chosen using propensity score matching and included in our study as a control group. The control group was matched to the study group regarding the timing of transplantation, demographics, and all variables except experiencing AR. Required data were collected and genetic analysis for the selected genetic polymorphisms was performed for all patients. Data were analyzed. The results of the current study could be concluded as follows: -CTLA-4 polymorphism rs3087243 (+6230 A/G) as a promising biomarker for kidney allograft rejection with significant impact on graft survival, particularly for TCMR Banff graded ≥ 1. -CD 28 polymorphism rs3116496 (IVS3 + 17T/C) and CD 86 polymorphism rs1129055 (+1057G>A) showed non-significant association with AR and graft survival. -PD-1.3 polymorphism rs2227982 (+7146 G > A) showed variant of unknown significance. Key Words ( not more than 10 ) : Acute renal allograft rejection- Bannf classification- Kidney transplantation – Single nucleotide polymorphism