RESUMO
The involvement of the human leukocyte antigen (HLA) in liver graft acceptance is controversial, but the frequency of acute rejection (AR) remains high in spite of the use of the modern immunosuppressive agents. The present study was aimed at determining whether an association exists between liver recipient HLA-C polymorphism and AR development that could influence graft acceptance. Four hundred and forty-six liver recipients and 473 controls were studied within the framework of a collaborative study carried out by the Spanish Transplant Immunotolerance Group (RED-GIT). HLA-A and -B were typed by the standard microlymphocytotoxicity technique, and HLA-C by polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP). A statistically significant decrease in the HLA-Cw*07 allele frequency was found in liver recipients suffering AR episodes compared to those without AR (NAR). Studies regarding the possible influence of the Asn80 and Lys80 epitopes showed that the Asn80 epitope also could be associated with AR. However, further analysis considering Asn80 alleles others than HLA-Cw*07, confirmed that the apparent protective effect of the Asn80 epitope was actually from the HLA-Cw*07 allele. In conclusion, the HLA-Cw*07 allele carried by the liver recipient is negatively associated with AR development, and could be considered a predictive factor for liver graft acceptance.
Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA-C/administração & dosagem , Antígenos HLA-C/genética , Transplante de Fígado/imunologia , Doença Aguda , Alelos , Feminino , Rejeição de Enxerto/genética , Antígenos HLA-C/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Cytokines are known to be important mediators during liver graft outcome and their gene polymorphism could affect the overall expression and secretion of cytokines. In this retrospective study, we analyzed the effect of TGF-beta1 polymorphism in 150 liver allograft recipients. Genotyping PCR-SSP were performed for TGF-beta1 gene (codon 10T/C and 25C/G). TGF-beta1 polymorphism at codon 10 and 25 correlate borderline with liver graft acceptance and when the combination between codon 10 and 25 was analyzed, it revealed that T/T G/C genotype and the TC haplotype were significantly associated with graft acceptance (p<0.05). TGF-beta1 high secretor phenotype was also increased in the acute rejection group close to significance (p=0.06). In conclusion, these findings show a correlation between TGF-beta1 gene polymorphism and liver graft acceptance.