ATG-induced accelerated immune senescence: clinical implications in renal transplant recipients.

Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.

Subclinical Epstein-Barr virus viremia among adult renal transplant recipients: incidence and consequences.

The natural history and clinical significance of posttransplant Epstein-Barr virus (EBV) infection remain largely unknown. The aims of this study are to describe the incidence, risk factors and consequences of EBV infection after kidney transplantation. A total of 383 consecutive patients having received a kidney transplant between January 2002 and December 2010 were included. EBV polymerase chain reaction (PCR) was performed every 2 weeks for 3 months, and every 4 weeks for the next 9 months. A total of 155 of the 383 patients (40%) had at least one positive viremia during the first year posttransplant. The median time to viremia was day 31 posttransplant (14-329). A total of 73 (47%) had EBV viremia > 10(3) log and 23 (15%) had positive viremia for more than 6 months. EBV D+/R- patients (12/18 (67%) versus 143/365 (39%), p = 0.02) and those having received antithymocyte globulins (ATG) (54% vs. 35%; p<0.001) were more likely to develop EBV infection. EBV infection (hazard ratio [HR], 3.03; 95% confidence interval [CI], 1.72-8.29; p = 0.01) was associated with the occurrence of opportunistic infections. A positive EBV PCR during the first 6 months posttransplant was associated with graft loss (HR, 3.04; 95% CI, 1.36-6.79; p = 0.014). EBV reactivation is frequent after transplantation and reflects overimmunosuppression. Prospective studies should examine the association between EBV and graft loss.