140. Lytic and Latent EBV Gene Expression in Transplant Recipients with and Without Post-Transplant  Lymphoproliferative Disorder
Session: Oral Abstract Session: Clinical Virology and Treatment
Friday, October 21, 2011: 9:15 AM
Room: 156ABC
Background: Epstein-Barr virus (EBV) is associated with Post-transplant lymphoproliferative disorder (PTLD), which has significant morbidity and mortality in transplant recipients. To devise prophylactic measures, we need predictors of PTLD and a better understanding of the physiopathogenesis of the disease. In this study, we evaluated the ratio between latent and replicating EBV nucleic acids in individuals with PTLD by comparison with transplant recipients without PTLD and immunocompetent hosts with EBV DNA-emia.

 Methods: Subjects were prospectively identified between July 2009 and October 2010 at the University of Colorado Hospital including 7 transplant recipients with PTLD, 105 transplant recipients without PTLD and 69 immunocompetent hosts.  We established and validated a method for total RNA extraction from frozen whole blood samples. RNA was successfully amplified in samples with EBV DNA ≥3600 copies/ml.   EBV DNA, LMP-2A and BZLF1 mRNAs were quantified using real-time  PCR.

 Results: We found that PTLD subjects had significantly higher EBV DNA-emia ( mean±SEM: 875,806±397,632) compared with non-transplant immunocompetent subjects (mean±SEM : 32,901± 8,757; p <0.0001), and transplant recipients without PTLD (mean±SEM: 94,577±22,960; p<0.0001). The ratios between LMP-2A and BZLF1 mRNA in transplant recipients were significantly lower than in non-transplant subjects (12±1 vs.16± 2; P =0.04), suggesting transplant recipients had higher proportions of replicating virus contributing to EBV DNA-emia than immunocompetent hosts . However, transplant recipients with and without PTLD displayed similar ratios (14±2 vs 12±1; p=0.37).

Conclusion: These results suggest that EBV replication makes a larger contribution to the circulating EBV DNA in transplant recipients compared with immunocompetent hosts. Transplant recipients seem to lose control over EBV replication, which may contribute to the development of PTLD. Use of antivirals could be beneficial to patients at risk of developing PTLD.


Subject Category: O. Transplant infectious diseases

Jing Kroll, MD1, Shaobing Li, MD2, Marilyn Levi, MD2 and Adriana Weinberg, MD3, (1)Internal Medicine, University of Colorado Denver, Aurora, CO, (2)University of Colorado Denver, Aurora, CO, (3)University of Colorado Anschutz Medical Campus, Aurora, CO

Disclosures:

J. Kroll, None

S. Li, None

M. Levi, None

A. Weinberg, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.