A PROSPECTIVE-STUDY IN HEART AND LUNG-TRANSPLANT RECIPIENTS CORRELATING PERSISTENT EPSTEIN-BARR-VIRUS INFECTION WITH CLINICAL EVENTS

Background, A 2-year prospective study was set up with 30 cardiothorac ic transplant recipients to study Epstein-Barr virus (EBV) infection a nd immunity and their correlation with clinical events, Methods. Regre ssion assays were used to measure EBV-specific cytotoxic T lymphocyte (CTL) function, Tissue culture, immunoblotting, and polymerase chain r eaction were used for EBV detection and isolate variation studies. Res ults. CTL activity was significantly lower in pretransplant seropositi ve patients than in healthy controls (P < 0.001). CTL response was und etectable in all patients during the first 6 months after transplantat ion, but returned at, levels significantly lower than pretransplant an d control levels during-the second posttransplant year (P < 0.001). Re turn of CTL function was directly correlated with time of last treated rejection episode (P < 0.003) and duration of high plasma levels of c yclosporine (over 400 ng/ml; P < 0.003). Significantly higher levels o f EBV were detected in peripheral blood during the first 6 months than in pretransplant or control samples (P < 0.05). Excretion of EBV in t hroat washings was significantly lower daring the first 3 months when all patients were receiving acyclovir than in pretransplant and contro l samples (P = 0.02), An increase in virus shedding was noted 3-6 mont hs after transplantation, which was significantly higher than in pretr ansplant patients and controls (P < 0.05). Comparison of recipients' a nd donors' virus isolates in 11 cases showed that seropositive recipie nts retained their original EBV isolate and did not acquire the donor virus. Conclusions. Immunosuppression decreased EBV-specific host immu ne function, which in turn favored increased EBV load in peripheral bl ood and increased excretion in the oropharynx. The transfer of donor v irus to the seropositive recipients was not observed.