Abstract
BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.
Highlights
Immunosuppressive drugs, such as cyclosporine A (CsA), tacrolimus (TAC), mycophenolate mofetil (MMF) or prednisone (Pred), are typically administered to renal transplant patients to prevent graft rejection
Baseline characteristics of 304 renal transplant recipients A total of 304 patients were recruited to the study, including 192 male and 112 female cases
No significant differences in age, sex, primary disease, human leukocyte antigen mismatches, blood transfusion, renal transplantation or immunosuppressant regimen were found between patients with infection and those without (Table 1)
Summary
Immunosuppressive drugs, such as cyclosporine A (CsA), tacrolimus (TAC), mycophenolate mofetil (MMF) or prednisone (Pred), are typically administered to renal transplant patients to prevent graft rejection. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a critical negative regulator of the T cell-mediated immune response and a key element that induces immune tolerance in the immune system [6]. It is expressed constitutively on the surface of regulatory T cells (Tregs); it is detectable on approximately 50% of Tregs, but found on only ,1% of naive helper T cells [7]. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown
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