D. Kewalramani1, M. Ningappa1, R. Sindhi1, M. Paul1, G. Mazariegos1, K. Soltys1, G. Bond1, A. Ganoza1, A. Khanna1, C. Ashokkumar1 1Childrens Hospital of Pittsburgh of UPMC, Department Of Pediatric Surgery, Pittsburgh, PENNSYLVANIA, USA
Introduction:
Epstein-Barr viral (EBV) infection is a common sequelae of immunosuppression after liver or intestine transplantation (Tx) and can transform to post-transplant lymphoproliferative disease (PTLD). Prior exposure of the donor or recipient to EBV can facilitate EBV reactivation and infection but is not always predictive of infection.
Methods:
To determine the role of cell-mediated immunity in predicting EBV viremia and PTLD, we stimulated peripheral blood mononuclear cells (PBMC) from 36 children with Tx and 29 healthy adults age 21 years or more, overnight with EBV viral lysate. We measured the frequency (%) of EBV-specific T-cells that expressed CD154, a surrogate for IFN-gamma in viral antigen-specific T-cells with flow cytometry. EBV viral load was measured as viral genome copies/ ml with PCR at defined intervals per surveillance protocol.
Results:
Among healthy controls, median EBV-specific T-cell frequencies were 31.5±2.6 with IQR 18.95. Among Tx children, median age was 13.6 (1.0 to 31 years) and median (IQR) EBV-specific T-cell frequencies before and after Tx were lower at 14.7 (13.6) p<0.001, and 6.6 (20.8) p<0.001, respectively when compared with healthy controls.
Among the 10 Tx children sampled before transplantation, median EBV-specific T-cell frequencies were 14.7%. Peak viral loads developed earlier 56 (0-83) vs 491 (66-922) days post-transplant, p=0.052, Fisher’s exact test, and median viral loads were numerically higher at 33,000 vs 2500, p=NS, in 5 children with EBV-specific T-cells 14.7% or less, compared with the remaining 5 with frequencies >14.7%.
Among the 26 remaining Tx children, post-transplant samples were obtained at 731 days (range 11-9120 days) after Tx. Five of 16 children with EBV-specific T-cell frequencies of 14.7% or less were found to have PTLD. PTLD did not occur among the 10 Tx children sampled after transplant who had EBV-specific T-cells >14.7%.
Conclusion:
EBV-specific T-cells offer protection from EBV viremia and EBV-related PTLD and can be used to guide management of immunosuppression when viremia or PTLD appear after liver or intestine transplantation in children.