Quantitative tissue polymerase chain reaction for Epstein-Barr virus in pediatric solid organ recipients

Background: Infections caused by herpes virus, in particular, Epstein-Barr virus (EBV), remain a major challenge in solid organ transplantation. Little is known about the significance of tissue EBV load. Methods: Twenty-three tissue biopsy specimens (19 kidney, 3 gastrointestinal, and 1 tonsil specimen) and 2 bronchoalveolar lavage specimens from 14 pediatric transplant recipients (10 kidney, 3 liver, 1 combined transplant) were subject to tissue EBV polymerase chain reaction (PCR) semiquantitative analysis and enzyme-linked immunosorbent assay (ELISA) methods. Results of biopsies were correlated with clinical data. Results: Five of 14 patients had clinically diagnosed EBV disease: 2 patients presented with a septic picture with multiorgan failure and pneumonitis; 1 patient had mononucleosis; 1 patient had an increase in serum creatinine level, lymphadenopathy, and chronic fatigue; and 1 patient had EBV nephritis. These 5 patients underwent 12 biopsies at the time of clinically active infection; 8 biopsies had positive results (up to 111 copies/10 muL of extracted DNA). Conversely, 1 of the remaining 13 tissue biopsy specimens from asymptomatic patients had positive results on ELISA, but undetectable viral load, whereas 8 patients had a positive EBV immunoglobulin G titer with historic evidence of EBV replication in the blood. No patient without evidence of EBV had positive EBV tissue PCR results. Conclusion: Increased EBV load was found in more than 50% of patients, pointing to a previously underrecognized importance of EBV detection in tissues from transplant recipients. The presence of EBV in tissue correlated with the presence of viremia, whereas tissue PCR had 100% specificity. EBV load should be included in biopsy evaluation.