RESUMEN
As chemokines and adhesion molecules play major roles in the process by which leukocytes are recruited from the bloodstream into sites of inflammation, genetic variations in the production or activity of molecules may influence susceptibility to acute rejection episodes. This study sought to determine the impact of recipient monocyte chemoattractant protein-1 (MCP-1), chemokine receptor (CCR2, CCR5), and adhesion molecule (ICAM-1, PECAM-1 and L/E selectin) polymorphisms on acute rejection after renal transplantation. We selected 169 healthy blood donors and 173 renal transplant recipients for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. Using molecular methods DNA was genotyped for 11 polymorphisms of these inflammatory molecules genes. Results were stratified by the incidence of rejection episodes and by human leukocyte antigen (HLA) mismatching. No association was detected between adhesion molecule polymorphisms and the incidence of acute rejection episodes. However, a significant risk of acute renal loss was observed among HLA-identical recipients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence interval, 0.05 to 1.06; P=.035). In conclusion, the observed association of CCR2-64I with acute rejection episodes should be added to the spectrum of immunogenetic factors known to be involved in renal allograft rejection.
Asunto(s)
Quimiocinas/metabolismo , Trasplante de Riñón/métodos , Polimorfismo Genético , Receptores CCR2/genética , Adulto , Alelos , Donantes de Sangre , Femenino , Rechazo de Injerto , Antígenos HLA/metabolismo , Humanos , Inflamación , Fallo Renal Crónico/genética , Fallo Renal Crónico/terapia , Masculino , TúnezRESUMEN
Acute rejection is the main cause of early renal allograft failure. Adhesion molecules provide signals for activation and recruitment of effector cells leading to graft infiltration by host T cells, which are key to allograft rejection. This study was undertaken to analyze the adhesion molecule gene polymorphisms in renal transplant recipients and to investigate their potential association with the development of acute allograft rejection. A total of 120 renal transplant recipients and 100 controls were retrospectively genotyped. Seven nucleotide polymorphisms in intracellular adhesion molecule (ICAM)-1, platelet endothelial cell adhesion molecule (PECAM)-1, L-selectin, and E-selectin were analyzed using allele-specific polymerase chain reaction (PCR)-SSP assay and PCR-restriction fragment length polymorphism (RFLP). Recipients were selected on the basis of the development of acute allograft rejection in the first 6 months after renal transplantation. Forty-one patients developed acute allograft rejection and 79 showed uneventful courses. There was no evidence for an association of any polymorphism with acute rejection. Thus, we concluded that these genes do not predispose to acute renal allograft rejection.