Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients

Abstract

Summary Development of Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real‐time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty‐seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1–16.9) years post‐HTX]. In follow‐up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 ± 70.2 vs. 119.6 ± 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.

Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease

“…A link between EBV load and level of immunosuppression in adult HT patients was noted[23]. We hypothesize that reduction of immunosuppression has probably contributed for higher allograft rejection episodes in patients with high EBV load.…”

EBV viral load detection in clinical virology

“…[60][61][62] Routine EBV VL monitoring, particularly in patients experiencing primary infection after transplant, has also been recommended as a surrogate marker of immunosuppression and resulting PTLD risk in clinical trials of new immunosuppressives. 63 Preliminary reports suggesting or examining tailoring of individual immunosuppression based on EBV VL load with a goal of improving graft outcomes have recently been published results.…”

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

“…They speculate that EBV load serves as a functional marker of the degree of immunosuppression and that undetectable EBV implies underimmunosuppression and associated risk of rejection (5). A link between viral load and level of immunosuppression in heart transplant patients was noted as well (43).…”

“…While whole blood more frequently contains amplifiable EBV DNA than does plasma, it would be inappropriate to conclude that whole blood is more informative than plasma for assessing PTLD status. Indeed, healthy transplant recipients often have low-level EBV DNA in whole blood with or without EBV DNA in the plasma fraction, and only a small proportion of these patients progress to PTLD (16,43,78,99,193). A practical advantage of whole blood is that it saves labor compared to preparing plasma by centrifugation.…”