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 cardiothoracic transplant recipients to study Epstein-Barr virus (EBV) infection and immunity and their correlation with clinical events.


METHODS
Regression assays were used to measure EBV-specific cytotoxic T lymphocyte (CTL) function. Tissue culture, immunoblotting, and polymerase chain reaction were used for EBV detection and isolate variation studies.


RESULTS
CTL activity was significantly lower in pretransplant seropositive patients than in healthy controls (P<0.001). CTL response was undetectable in all patients during the first 6 months after transplantation, but returned at levels significantly lower than pretransplant and control levels during the second posttransplant year (P<0.001). Return of CTL function was directly correlated with time of last treated rejection episode (P<0.003) and duration of high plasma levels of cyclosporine (over 400 ng/ml; P<0.003). Significantly higher levels of EBV were detected in peripheral blood during the first 6 months than in pretransplant or control samples (P<0.05). Excretion of EBV in throat washings was significantly lower during the first 3 months when all patients were receiving acyclovir than in pretransplant and control samples (P=0.02). An increase in virus shedding was noted 3-6 months after transplantation, which was significantly higher than in pretransplant patients and controls (P<0.05). Comparison of recipients' and donors' virus isolates in 11 cases showed that seropositive recipients retained their original EBV isolate and did not acquire the donor virus.


CONCLUSIONS
Immunosuppression decreased EBV-specific host immune function, which in turn favored increased EBV load in peripheral blood and increased excretion in the oropharynx. The transfer of donor virus to the seropositive recipients was not observed.
Haque
T
T
Department of Medical Microbiology, The University of Edinburgh Medical School, United Kingdom.
Thomas
J A
JA
Parratt
R
R
Hunt
B J
BJ
Yacoub
M H
MH
Crawford
D H
DH
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D016041:Heart-Lung Transplantation / Q000276:immunology*; D006566:Herpesviridae Infections / Q000453:epidemiology* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007223:Infant; D016030:Kidney Transplantation / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011446:Prospective Studies; D012016:Reference Values; D012044:Regression Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000276:immunology
D004279:DNA, Viral