RESUMO
Complement-mediated humoral rejection has become the main focus of research in organ transplantation. The aim of this study was to investigate the possible association of the complement C5aR gene 450 C/T polymorphism in antibody-mediated renal allograft rejection. This polymorphism was investigated in 290 first deceased donor kidney graft recipients with well functioning grafts and no rejection treatment during the first transplant year (WFG), 265 recipients with graft failure within the first transplant year (F), and 187 healthy controls. Frequency of the 450 CT genotype was lower in the total population of 555 kidney recipients (4.7%) than in 187 healthy controls (8.6%), but the difference was not statistically significant (P = 0.065). A significantly higher frequency of CT genotype was found in F patients (CT: 6.8%) when compared to WFG patients (CT: 2.8%, P = 0.027). The CT genotype was also significantly lower in WFG patients than in healthy controls (P = 0.009). Low frequency of the C5aR 450 CT genotype, which apparently is a feature of certain kidney diseases, appears to be associated with good graft outcome in kidney transplantation and might be helpful for identifying recipients who are at low risk for graft rejection.
Assuntos
Transplante de Rim , Polimorfismo de Nucleotídeo Único/genética , Receptor da Anafilatoxina C5a/genética , Transplantados , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Natural killer (NK) cell function can be modulated by the killer cell immunoglobulin-like receptors (KIR) which interact with human leukocyte antigen (HLA) class I molecules on target cells. KIR-ligand mismatching has recently been shown by van Bergen et al. (American Journal of Transplantation 2011; 11(9): 1959-1964) to be a significant risk factor for long-term graft loss in HLA-A, -B and -DR compatible kidney transplants. To verify this potentially important finding, we performed genotyping of 608 deceased-donor kidney graft recipients and their HLA-A, -B and -DR compatible donors for KIR and HLA, using samples and clinical data provided by the Collaborative Transplant Study. Graft survival of KIR-ligand-matched and -mismatched transplants was compared. We found no impact of KIR-ligand mismatching on 10-year graft survival in HLA-A, -B, -DR compatible kidney transplants. Further analysis did not reveal a significant effect of recipient activating/inhibitory KIR or KIR genotypes on graft survival. Our data do not support the concept that KIR-HLA matching might serve as a tool to improve long-term renal allograft survival.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Transplante de Rim/métodos , Receptores KIR/metabolismo , Insuficiência Renal/imunologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Genótipo , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal/cirurgia , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
In hematopoietic stem cell transplantation (HSCT), disparities between recipients and donors for minor histocompatibility antigens (mHags) have been shown to be related to graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. We investigated the effect of mHag mismatches on kidney allograft survival. Out of 33 785 kidney transplants on which DNA and clinical data were available to the Collaborative Transplant Study (CTS), 702 recipient/donor pairs could be identified as HLA-A, -B and -DRB1 matched first transplants of Caucasian origin. These pairs were typed for genetic polymorphisms of the mHags HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1 and UGT2B17. Because mHags are presented in an HLA-restricted manner, only HLA-A*02 positive pairs were included in the analysis of HA-1, HA-2 and HA-8. Similarly, only HLA-A*01, HLA-B*44 and HLA-A*24 positive pairs were considered for the evaluation of HA-3, HB-1 and ACC-1, respectively, whereas UGT2B17 compatible transplants were assessed in HLA-A*29 and HLA-B*44 positive pairs. None of the mHag disparities showed a statistically significant effect on death-censored 5-year graft survival. This report represents the first large-scale study on the relevance of mHags in kidney transplantation.
Assuntos
Transplante de Rim/imunologia , Antígenos de Histocompatibilidade Menor/fisiologia , Frequência do Gene , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Imunofenotipagem , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/imunologia , Estudos RetrospectivosAssuntos
Doenças Transmissíveis/diagnóstico , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Complicações Pós-Operatórias/diagnóstico , Biomarcadores/sangue , Doenças Transmissíveis/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão/métodos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-10/sangue , Transplante de Rim/patologia , Valor Preditivo dos Testes , Fatores de Risco , Subpopulações de Linfócitos T/imunologiaRESUMO
The incidence of non-Hodgkin's lymphoma was analysed in over 70,000 kidney transplant recipients and over 10,000 heart, heart-lung or lung transplant recipients. An increased incidence of lymphomas during the first posttransplant year was observed in cadaver kidney recipients as compared to related kidney recipients, in thoracic organ recipients as compared to kidney recipients, in heart-lung recipients as compared to heart or lung recipients, in patients transplanted in North America as compared to patients transplanted in Europe, in patients receiving cyclosporine in combination with azathioprine as compared to patients with other immunosuppressive regimens, and in patients receiving ATG/ALG or monoclonal OKT3 for rejection prophylaxis.