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. 2000 Feb;38(2):613-9.
doi: 10.1128/JCM.38.2.613-619.2000.

High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders

F Baldanti  1 , P Grossi, M Furione, L Simoncini, A Sarasini, P Comoli, R Maccario, R Fiocchi, G Gerna
Affiliations

High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders

F Baldanti et al. J Clin Microbiol. 2000 Feb.

Abstract

Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of >1, 000 genome equivalents (GE)/0.5 microg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), >/=5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by >/=1 log(10) unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

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Figures

FIG. 1
FIG. 1
Construction of the standard curve. (A) pP3 copy number, ranging from 10,000 to 1 (external standards); pRM, 100 copies for each sample (internal control). MW, molecular weight markers (pBR322 cleaved with HaeIII). (B) Standard curve obtained by densitometric analysis of gel signals. (C) Example of EBV DNA quantification in sequential PBMC samples from patient (pt) 5 (from left to right, 7,420, 11,520, and 70 GE) and pt 9 (from left to right, 1,200, 3,980, and 38,900 GE) (see Table 3).
FIG. 2
FIG. 2
EBV DNA levels in the blood of the three population groups studied. Median levels are indicated by horizontal lines. Statistical differences between groups are given at the top.
FIG. 3
FIG. 3
Follow-up of EBV DNA levels in 32 SOT recipients with asymptomatic EBV infections. (A) EBV DNA levels (means ± standard deviations) in 19 patients consistently showing <1,000 GE during follow-up (■) and in 10 patients with at least one blood sample in the range of 1,000 to 5,000 GE during follow-up (□). (B) Individual fluctuations of EBV DNA levels in three patients showing ≥5,000 GE in the blood at least once during follow-up.
FIG. 4
FIG. 4
Effect of modulation of immune-suppressive therapy on EBV DNA levels in the blood of four SOT recipients with symptomatic EBV infections (see Table 3). The vertical dotted line indicates the initial time of reduction of the immunosuppressive regimen. pt, patient.
FIG. 5
FIG. 5
Parallel reductions in FK506 plasma levels and the EBV DNA load in the blood of an SOT recipient (patient 9 [see Table 3]) with a symptomatic EBV infection.
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