Impact of Immunosuppressive Therapy on Anti-EBV Specific CD8+T-Cells in Pediatric Heart Transplant Recipients

Abstract

Purpose Epstein Barr Virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) is a severe complication in pediatric heart transplant (HTX) patients. Risk factors for PTLD include EBV-seronegativity at time of HTX, type and degree of immunosuppression (IS) and chronically high EB viral load in peripheral blood. CD8+ cytotoxic EBV-specific T-lymphocytes are important to control EBV-infection and persistence, which can be measured by enyzme linked immunspot (Elispot). Methods and Materials In this study we prospectively monitored Epstein Barr viral load by quantitative PCR and CD8+ T-cell response against from the latent and lytic EBV antigens using the Elispot assay in pediatric HTX patients in regard to their immunosuppressive therapy. EBV-specific T-cells were measured as spot forming units (SFU). Patients with CyA-MMF and CyA-Everolimus were compared in a subanalysis. Results 39 pediatric heart transplant patients were repeatedly measured with a median age of 13,8 years (range: 2,9-26,5). Median time post-TX was 7,5 years (range: 0,2-17,5). Patients with CyA-MMF showed significant increased EBV-specific CD8+T-cells against latent (55 vs. 26, p=0.04) and lytic (20 vs 4, p= 0.02) antigens if compared with CyA-Everolimus. Patients with CyA-MMF showed a reduced EBV-activity (Mean viral load 470± 241 vs. 59543± 39120 copies/ml, p=0.001). Conclusions CyA-MMF and not CyA-EVE seems to improve EBV-specific CD8+ T-cells response in pediatric heart transplant recipients with same exposure from CyA. A decreased response to lytic antigens is indicative for an increased of PTLD in high viral load carriers in this cohort.