![[Feedback]](/icons/banner/feedbackACT.gif)
![[For Subscribers]](/icons/banner/subscriberACT.gif)
![[Archive]](/icons/banner/archiveACT.gif)
![[Search]](/icons/banner/searchACT.gif)
![[Contents]](/icons/banner/tocACT.gif)
Previous Article | Next Article 
Journal of Clinical Microbiology, April 1999, p. 1113-1116, Vol. 37, No. 4
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Detection of Epstein-Barr Virus DNA in Sera from
Transplant Recipients with Lymphoproliferative Disorders
Ajit P.
Limaye,1,*
Meei-Li
Huang,2
Ederlyn E.
Atienza,2
James M.
Ferrenberg,2 and
Lawrence
Corey2
Department of Laboratory Medicine & Medicine
(Infectious Diseases), University of
Washington,1 and Program in Infectious
Diseases, Fred Hutchinson Cancer Research
Center,2 Seattle, Washington 98195-7110
Received 9 October 1998/Returned for modification 7 December
1998/Accepted 13 January 1999
 |
ABSTRACT |
Early diagnosis of Epstein-Barr Virus (EBV)-associated
posttransplant lymphoproliferative disease (PTLD) is important because many patients respond to reduction in immunosuppression, especially if
PTLD is detected at an early stage. Previous studies have
found elevated EBV DNA levels in blood from patients with PTLD, but these assays required isolation of cellular blood fractions and quantitation. We evaluated the presence of cell-free EBV DNA in serum
from solid-organ transplant recipients as a marker for PTLD. Five of 6 transplant recipients with histopathologically documented PTLD had EBV
DNA detected in serum at the time of diagnosis (sensitivity = 83%), compared with 0 of 16 matched transplant recipients without PTLD
(specificity = 100%) (P < 0.001 [Fisher's
exact test]). Furthermore, EBV DNA was detected in serum 8 and 52 months prior to the diagnosis of PTLD in two of three patients for whom
stored sera were analyzed. Detection of EBV DNA in serum
appears to be a useful marker for the early detection of PTLD in
solid-organ transplant recipients. Further studies to define
the role of such assays in evaluating solid-organ transplant patients
at risk for PTLD are warranted.
| |
INTRODUCTION |
Posttransplant lymphoproliferative
disease (PTLD) is an uncommon but important cause of morbidity and
mortality in organ transplant recipients; it results from uncontrolled
Epstein-Barr virus (EBV)-induced proliferation of B cells in the
setting of immunosuppression (7, 11, 18, 28). Early
detection is critical, since reduction in immunosuppression may result
in regression of PTLD (5, 26). Given the close association
of EBV and PTLD, both invasive and noninvasive strategies have been
devised to monitor patients for EBV after transplantation (10, 13,
15, 17, 19, 20, 22-25, 29). Previous studies have reported high
levels of EBV DNA in the blood of patients with PTLD as determined by
assays designed to detect EBV DNA in peripheral blood lymphocytes (PBL) (9, 10, 15, 17, 22-25). The assays used in these studies required separation of lymphocytes and/or mononuclear cell fractions from whole blood. But, since latent EBV DNA is present in
EBV-seropositive persons, the demonstration of quantitative differences
between EBV DNA levels in patients with and without PTLD was required when this sample source was utilized.
We have sought to address some of these issues by evaluating whether we
could detect EBV DNA directly from serum and by analyzing sequentially
collected sera from transplant recipients who subsequently did or did
not develop PTLD. We hypothesized that detection of EBV DNA in
acellular specimens (i.e., serum) would occur only for patients with
very high systemic EBV genome loads and thus might better differentiate
patients with PTLD from transplant recipients with low levels of EBV
reactivation as a result of immunosuppression.
| |
MATERIALS AND METHODS |
Patients and specimens.
All recipients of abdominal (kidney,
pancreas, liver) transplants with histopathologically confirmed PTLD
were identified prospectively during the study period (1 January 1996 through 30 June 1998) at the University of Washington Medical Center
(Seattle). PTLD was diagnosed according to previously published
clinical and histologic criteria (16, 19). All biopsy
specimens were analyzed by routine histochemical stains, flow cytometry
(cell surface markers and determination of clonality), and both
immunocytochemistry and in situ hybridization for EBV-specific products
as previously described (4, 16, 19, 27).
Six patients were diagnosed with PTLD during the study period, and in
each case, a sample of serum or plasma was obtained within 1 week of
the diagnosis of PTLD and stored at 
70°C until analyzed. Control
patients included 16 transplant recipients who were matched with regard
to the organ transplanted, pretransplant EBV serostatus, and
immunosuppressive regimen used. Each control patient had a minimum of 1 year of follow-up (or until death) after the date of the last serum
sample collection to determine whether PTLD had developed.
A total of 23 serum samples from the 6 case patients with PTLD and 87 serum samples from the 16 matched, control patients were analyzed. The
collection dates of the 23 samples from the case patients ranged from 0 to 79 months posttransplant (median of 5.5 months posttransplant),
while those from the control patients ranged from 0 to 72 months
posttransplant (median of 4 months posttransplant). Five of the 6 case
patients (83%) and 15 of the 16 control patients (94%) were EBV
seropositive at the time of transplant.
EBV PCR.
All PCR analysis was performed by persons who were
blinded to the clinical status of the patient whose sera were being
analyzed (i.e., PTLD case versus control). The EBV PCR assay was
performed as previously described (12). DNA was extracted
from 200 µl of serum by using the QIAamp blood kit (Qiagen) and was
eluted with 100 µl of 10 mM Tris (pH 8.0). Ten microliters of DNA was used for each PCR. Primers EBER1-A and EBER1-B (GTT TTG CTA GGG AGG AGA CG and GAC CGA AGA CGG CAG AAA GC,
respectively) were used to amplify a 118-bp region of EBER1
(1). Each 100-µl PCR mixture contained 50 mM KCl; 1.5 mM
MgCl2; 10 mM Tris-HCl (pH 8.4); 2 U of AmpliTaq DNA
polymerase (Perkin-Elmer, Foster City, Calif.); 200 µM (each) dGP,
dATP, and dCTP; 400 µM dUTP (Pharmacia); a 0.83 µM concentration of
each primer; 10 µl of glycerol; and 10 µl of purified DNA template.
PCR conditions were as follows: 96°C for 2 min; 35 cycles of 94°C
(30 s), 54°C (30 s), and 72°C (30 s); and 72°C for 5 min. The
EBER1-A-EBER1-B PCR product was detected by liquid hybridization with
32P-labeled probe, EBER1-P (GAC ACC GTC CTC ACC ACC
CG) (12). Seven microliters of PCR product and the
probe (106 cpm) were heated in 25 µl of a solution containing 1.2 M
NsCl, 100 µM each deoxynucleoside triphosphate, and 44% formamide at
97°C for 5 min. Ten-microliter samples of cooled hybridization
products were analyzed on 6% acrylamide gels, dried, and then
autoradiographed. To ensure that negative results were not due to
nonspecific inhibition of PCR, each PCR product was spiked with 50 copies of EBER-fly2 DNA. EBER-fly2 is identical to the EBER1-A-EBER1-B
PCR product except that the EBER1-P probe sequence is replaced by 21 bp
of Drosophila DNA (6). Each EBER1-A-EBER1-B PCR
product was also hybridized with 32P-labeled fly probe,
electrophoresed, and then autoradiographed. All the negative
EBER1-A-EBER1-B PCR results required detection of EBER-fly2 DNA. To
monitor for false positives, specimens were processed in parallel with
aliquots of phosphate-buffered saline. PCR mixtures without DNA were
also included in each PCR run. To ensure reproducibility of the PCR
result, each specimen was run in duplicate and the assay was repeated
for each specimen.
Statistical analysis.
Fisher's exact test on a
two-dimensional contingency table was used to compare the EBV PCR assay
results for patients with PTLD and control patients.
| |
RESULTS |
Six patients were diagnosed with PTLD during the study period; the
clinical characteristics of these patients are shown in Table
1. Five of the six patients were EBV
seropositive prior to transplant. The time of diagnosis of PTLD ranged
from 7.5 months to 79 months after transplant. All biopsy specimens met
criteria for PTLD (16, 19), and all specimens were
determined to contain EBV-related products by immunocytochemistry
and/or in situ PCR.
EBV DNA was detected in the sera of 5 of 6 patients at the time of
diagnosis of PTLD. In contrast, EBV DNA was not detected in the serum
of any of the 16 matched control patients (P < 0.001 [Fisher's exact test]) (Table 2). The
single patient for whom EBV DNA was not detected in serum at the time
of diagnosis of PTLD presented with a solitary skin nodule and no
evidence of disease elsewhere (patient 5) (Table 1).
A total of 87 serum samples from 16 control patients were tested, and
all were negative for EBV DNA by our assay (Table 2). Stored sera from
three of the patients with PTLD were available for analysis, and the
results are shown in Table 3. For two of the three patients, EBV DNA was detectable in serum as early as 8 and
52 months prior to the diagnosis of PTLD (patients 1 and 3, respectively). For patient 2, only two stored serum samples were available, collected 13 and 19 months prior to the diagnosis of
PTLD, and both were negative for EBV DNA in our assay.
| |
DISCUSSION |
Noninvasive monitoring could theoretically be a useful
method for evaluating transplant patients at risk for developing PTLD and might provide a basis for the use of preemptive strategies, such as
reduction in immunosuppression or antiviral therapy, to reduce the
incidence and severity of PTLD after transplantation. Several studies
have assessed EBV DNA levels in transplant recipients with PTLD and
have demonstrated elevated levels in PBL from patients with PTLD
compared to controls (10, 15, 17, 19, 22-25, 29). All of
these studies used assays that required the separation of cellular
fractions from blood (i.e., either peripheral blood mononuclear cells
or PBL) and required quantitation. In the present study, a technically
simpler method of EBV DNA amplification directly from serum was used to
analyze samples from solid-organ transplant recipients with and without PTLD.
We evaluated the sensitivity of PCR in serum to provide a screening
method for PTLD, thereby obviating the need for both separation of
cellular fractions from whole blood and quantitation of levels if EBV
DNA was detected. We hypothesized that detection of EBV DNA in serum
(as opposed to PBL) would occur only for patients with relatively high
systemic EBV loads and thus would better differentiate transplant
recipients with and without PTLD than assays that measure EBV DNA
levels in PBL. Barkholt et al. published a study in which EBV DNA was
measured in the sera of a cohort of liver transplant recipients at risk
for developing PTLD (3). A nested-PCR assay was used, and
58% of all patients had detectable EBV DNA levels at some point within
the first 3 months posttransplant. The assay's sensitivity was such
that 33% of patients had EBV DNA detectable in serum even before liver
transplantation. Although EBV DNA was detected in the serum of all
three patients who subsequently developed PTLD, the high frequency of
EBV detection in patients without PTLD limited the assay's specificity
and clinical utility for predicting subsequent development of PTLD. In
contrast, we used a nonnested PCR and found that 0 of 87 sera from 16 control patients had detectable EBV DNA at various times after
transplant (specificity = 100%). Conversely, 5 of 6 prospectively
identified patients with PTLD had EBV DNA detected in serum at the time
of diagnosis (sensitivity = 83%). The only patient who was
negative in the assay at the time of PTLD diagnosis had a single
subcutaneous skin nodule (without any evidence of PTLD elsewhere by
clinical exam or total body imaging) as the sole manifestation of PTLD. In the only other study of EBV DNA detection in acellular specimens, Fontan and colleagues documented EBV DNA in serum of patients with
PTLD, but few details about the timing of the collection of the
positive serum samples relative to the time of diagnosis or clinical
characteristics of patients were provided (8).
If our findings are validated in larger studies, detection of serum EBV
DNA could prove to be useful for evaluating solid-organ transplant
patients with clinical syndromes compatible with PTLD. For example, two
of the patients in the present study presented with pulmonary nodules
and fever (patients 1 and 3). A variety of infectious and noninfectious
etiologies were considered, and detection of EBV DNA in sera from
these patients led us to temporarily reduce immunosuppression (as
empiric treatment for possible PTLD) until a definitive invasive
procedure (i.e., open lung biopsy) could be performed and the
diagnosis of suspected PTLD could be confirmed. In both cases, the
results of the serum EBV PCR were available before histopathologic
evaluation of the lung biopsy specimens. Thus, such an assay could
potentially serve as a useful adjunct to definitive histopathologic
evaluation for the early diagnosis of PTLD.
In addition to potentially serving as an adjunct to the early diagnosis
of PTLD, detection of EBV DNA in serum might be used to identify
patients at risk for developing PTLD. In the present study, we were
able to detect EBV DNA persistently in the sera of two of three
patients who subsequently developed PTLD, thereby supporting a role for
closely monitoring patients with EBV DNA detectable in serum. If our
results are validated in larger studies, routine monitoring for EBV DNA
in serum may provide a marker by which preemptive strategies are
implemented (e.g., antiviral therapy or reduction of
immunosuppression when EBV DNA is detected in serum). Only
randomized prospective trials will clarify the effectiveness of
such a strategy.
Several limitations of the present study should be noted. The numbers
of patients were relatively small, and larger studies validating our
results are necessary. Further, although the sera collected at the time
of PTLD diagnosis were from prospectively identified patients, the
other samples from the same patients were not necessarily collected at
identical times for all patients. Moreover, some cases of PTLD develop
after primary EBV infection, and acute EBV infection may be associated
with serum viremia and thus not necessarily predict subsequent
development of PTLD. This is an important consideration in the
pediatric transplant population, where a significant proportion of
patients are at risk for acquiring primary EBV infection.
In summary, we have used PCR to amplify EBV DNA directly from sera of
patients with PTLD and have evaluated the assay by using a group of
transplant recipients with and without PTLD. The ease of performance,
sensitivity, and specificity of the assay for the early detection of
PTLD appear to be promising, and further studies using this assay
for monitoring patients for PTLD after solid-organ transplantation are warranted.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: University of
Washington Medical Center, Dept. of Laboratory Medicine, Box 357110, 1959 N.E. Pacific St., Seattle, WA 98195-7110. Phone: (206) 598-2148. Fax: (206) 598-6189. E-mail: limaye{at}u.washington.edu.
| |
REFERENCES |
| 1.
|
Baer, R.,
A. T. Bankier,
M. D. Biggen,
P. L. Deininger,
P. J. Farrell,
T. J. Gibson,
G. Hatfull,
G. S. Hudson,
S. C. Satchwell,
C. Seguin, et al.
1984.
DNA sequence and expression of the B95-8 Epstein-Barr virus genome.
Nature
310:207-211[Medline].
|
| 2.
|
Bai, X.,
G. Hosler,
B. B. Rogers,
D. B. Dawson, and R. H. Scherermann.
1997.
Quantitative polymerase chain reaction for human herpesvirus diagnosis and measurement of Epstein-Barr virus burden in posttransplant lymphoproliferative disorder.
Clin. Chem.
43:1843-1849[Abstract/Free Full Text].
|
| 3.
|
Barkholt, L. M.,
H. Dahl,
M. Enbom, and A. Linde.
1996.
Epstein-Barr virus DNA in serum after liver transplantation surveillance of viral activity during treatment with different immunosuppressive agents.
Transplant. Int.
9:439-445[Medline].
|
| 4.
|
Chang, K. L.,
Y. Y. Chen,
D. Shibata, and L. M. Weiss.
1992.
Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues.
Diagn. Mol. Pathol.
1:246-255[Medline].
|
| 5.
|
Cherqui, D.,
C. Duvoux,
F. Plassa,
P. Gaulard,
M. Julien,
P. L. Fagniez,
D. Dhumearx,
M. Goossens, and J. P. Farcet.
1993.
Lymphoproliferative disorder of donor origin in a liver transplant recipient: complete remission after drastic reduction of immunosuppression without graft loss.
Transplantation
56:1023-1026[Medline].
|
| 6.
|
Cone, R. W.,
A. C. Hobson, and M.-L. W. Huang.
1992.
Coamplified positive control detects inhibition of polymerase chain reactions.
J. Clin. Microbiol.
30:3185-3189[Abstract/Free Full Text].
|
| 7.
|
Craig, F. E.,
M. L. Gulley, and P. M. Banks.
1993.
Posttransplantation lymphoproliferative disorders.
Am. J. Clin. Pathol.
99:265[Medline].
|
| 8.
|
Fontan, J.,
A. Bassignot,
C. Mougin,
J. Y. Cahn, and M. Lab.
1998.
Detection of Epstein-Barr virus DNA in serum of transplanted patients: a new diagnostic guide for lymphoproliferative diseases.
Leukemia
12:772[Medline].
|
| 9.
|
Green, M.,
J. Reyes,
N. Jabbour,
E. Yunis,
P. Putnam,
S. Todo, and D. Rowe.
1996.
Use of quantitative PCR to predict onset of Epstein-Barr viral infection and post-transplant lymphoproliferative disease after intestinal transplantation in children.
Transplant. Proc.
28:2759-2760[Medline].
|
| 10.
|
Kenagy, D. N.,
Y. Schlesinger,
K. Weck,
J. N. Ritter,
M. M. Gaudreault-Keener, and G. A. Storch.
1995.
Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease.
Transplantation
60:547-554[Medline].
|
| 11.
|
Khanna, R.,
S. R. Burrows, and D. J. Moss.
1995.
Immune regulation in Epstein-Barr virus-associated diseases.
Microbiol. Rev.
59:387-405[Abstract/Free Full Text].
|
| 12.
|
Koelle, D. M.,
M. L. Huang,
B. Chandran,
J. Vieira,
M. Piepkorn, and L. Corey.
1997.
Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates.
J. Infect. Dis.
176:94-102[Medline].
|
| 13.
|
Lager, D. J.,
H. Burgart, and D. D. Slagel.
1993.
Epstein-Barr virus detection in sequential biopsies from patients with a posttransplant lymphoproliferative disorder.
Mod. Pathol.
6:42-46[Medline].
|
| 14.
|
Lucas, K. G.,
R. L. Burton,
S. E. Zimmerman,
J. Wang,
K. G. Cornetta,
K. A. Robertson,
C. H. Lee, and D. J. Emmanuel.
1998.
Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation.
Blood
91:3654-3661[Abstract/Free Full Text].
|
| 15.
|
Martinez, O. M.,
J. C. Villanueva,
L. Lawrence-Miyasaki,
M. B. Quinn,
K. Cox, and S. M. Krams.
1995.
Viral and immunologic aspects of Epstein-Barr virus infection in pediatric liver transplant recipients.
Transplantation
59:519-524[Medline].
|
| 16.
|
Nalesnik, M. A.,
R. Jaffe,
T. E. Starzl,
A. J. Demetris,
K. Porter,
J. A. Burnham,
L. Makowka,
M. Ho, and J. Locker.
1988.
The pathology of post-transplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression.
Am. J. Pathol.
133:173-192[Abstract].
|
| 17.
|
Preiksaitis, J. K.,
F. Diaz-Mitoma,
F. Mirzayans,
S. Roberts, and D. H. Tyrrell.
1992.
Quantitative oropharyngeal Epstein-Barr virus shedding in renal and cardiac transplant recipients; relationship to immunosuppressive therapy, serologic responses, and the risk of posttransplant lymphoproliferative disorder.
J. Infect. Dis.
166:986-994[Medline].
|
| 18.
|
Purtilo, D. T.
1981.
Immune deficiency predisposing to Epstein-Barr virus-induced lymphoproliferative diseases: the X-linked lymphoproliferative syndrome as a model.
Adv. Cancer Res.
34:279[Medline].
|
| 19.
|
Randhawa, P. S.,
R. Jaffee,
M. Demetris,
M. Nalesnik,
T. E. Starzl,
Y. Y. Chen, and L. M. Weiss.
1991.
The systemic distribution of Epstein-Barr virus genomes in fatal post-transplantation lymphoproliferative disorders. An in situ hybridization study.
Am. J. Pathol.
138:1027-1033[Abstract].
|
| 20.
|
Randhawa, P. S.,
R. Jaffe,
A. J. Demetris,
M. Nalesnik,
T. E. Starzl,
Y. Y. Chen, and L. M. Weiss.
1992.
Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease.
N. Engl. J. Med.
327:1710-1714[Abstract].
|
| 21.
|
Randhawa, P. S.,
S. A. Yousem,
I. L. Paradis,
J. A. Dauber,
B. P. Griffith, and J. Locker.
1989.
The clinical spectrum, pathology, and clonal analysis of Epstein-Barr virus-associated lymphoproliferative disorders in heart-lung transplant recipients.
Am. J. Clin. Pathol.
92:177-185[Medline].
|
| 22.
|
Riddler, S. A.,
M. C. Breinig, and J. L. C. McKnight.
1994.
Increased levels of circulating Epstein-Barr-infected lymphocytes and decreased EBV nuclear antigen antibody responses are associated with the development of posttransplant lymphoproliferative disease in solid-organ transplant recipients.
Blood
84:972-984[Abstract/Free Full Text].
|
| 23.
|
Rooney, C. M.,
S. K. Loftin,
M. S. Holladay,
M. K. Brenner,
R. A. Krance, and H. E. Heslop.
1995.
Early identification of Epstein-Barr virus-associated post-transplantation lymphoproliferative disease.
Br. J. Haematol.
89:98-103[Medline].
|
| 24.
|
Rowe, D. T.,
L. Qu,
J. Reyes,
N. Jabbour,
E. Yunis,
P. Putnam,
S. Todo, and M. Green.
1997.
Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in the peripheral blood of pediatric transplant patients with lymphoproliferative disorders.
J. Clin. Microbiol.
35:1612-1615[Abstract].
|
| 25.
|
Savoie, A.,
C. Perpete,
L. Carpentier,
J. Joncas, and C. Alfieri.
1994.
Direct correlation between the load of Epstein-Barr virus-infected lymphocytes in the peripheral blood of pediatric transplant patients and risk of lymphoproliferative disease.
Blood
83:2715-2722[Abstract/Free Full Text].
|
| 26.
|
Starzl, T. E.,
K. A. Porter,
S. Iwatsuki,
J. T. Rosenthal,
B. W. Shaw,
R. W. Atchison,
M. A. Nalesnik,
M. Ho,
B. P. Griffith,
T. R. Hakala,
R. L. Hardesty, and R. Jaffe.
1984.
Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.
Lancet
i:583.
|
| 27.
|
Swerdlow, S. H.
1992.
Post-transplant lymphoproliferative disorders: a morphologic, phenotypic and genotypic spectrum of disease.
Histopathology
20:373-385[Medline].
|
| 28.
|
Thorley-Lawson, D. A.
1988.
Immunological responses to Epstein-Barr virus infection and the pathogenesis of EBV-induced diseases.
Biochim. Biophys. Acta
948:263-286.
|
| 29.
|
Weiss, L. M., and L. A. Movahed.
1989.
In situ demonstration of Epstein-Barr viral genomes in viral-associated B cell lymphoproliferations.
Am. J. Pathol.
134:651-659[Abstract].
|
Journal of Clinical Microbiology, April 1999, p. 1113-1116, Vol. 37, No. 4
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Hakim, H., Gibson, C., Pan, J., Srivastava, K., Gu, Z., Bankowski, M. J., Hayden, R. T.
(2007). Comparison of Various Blood Compartments and Reporting Units for the Detection and Quantification of Epstein-Barr Virus in Peripheral Blood. J. Clin. Microbiol.
45: 2151-2155
[Abstract]
[Full Text]
-
Lai, K. K.-Y., Cook, L., Krantz, E. M., Corey, L., Jerome, K. R.
(2005). Calibration Curves for Real-Time PCR. Clin. Chem.
51: 1132-1136
[Abstract]
[Full Text]
-
Schauer, E., Webber, S., Green, M., Rowe, D.
(2004). Surface Immunoglobulin-Deficient Epstein-Barr Virus-Infected B Cells in the Peripheral Blood of Pediatric Solid-Organ Transplant Recipients. J. Clin. Microbiol.
42: 5802-5810
[Abstract]
[Full Text]
-
Wadowsky, R. M., Laus, S., Green, M., Webber, S. A., Rowe, D.
(2003). Measurement of Epstein-Barr Virus DNA Loads in Whole Blood and Plasma by TaqMan PCR and in Peripheral Blood Lymphocytes by Competitive PCR. J. Clin. Microbiol.
41: 5245-5249
[Abstract]
[Full Text]
-
Andreone, P., Gramenzi, A., Lorenzini, S., Biselli, M., Cursaro, C., Pileri, S., Bernardi, M.
(2003). Posttransplantation Lymphoproliferative Disorders. Arch Intern Med
163: 1997-2004
[Abstract]
[Full Text]
-
Jenkins, F. J., Rowe, D. T., Rinaldo, C. R. Jr.
(2003). Herpesvirus Infections in Organ Transplant Recipients. CVI
10: 1-7
[Full Text]
-
Rose, C., Green, M., Webber, S., Kingsley, L., Day, R., Watkins, S., Reyes, J., Rowe, D.
(2002). Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization. J. Clin. Microbiol.
40: 2533-2544
[Abstract]
[Full Text]
-
Lei, K. I. K., Chan, L. Y. S., Chan, W.-Y., Johnson, P. J., Lo, Y. M. D.
(2002). Diagnostic and Prognostic Implications of Circulating Cell-free Epstein-Barr Virus DNA in Natural Killer/T-Cell Lymphoma. Clin. Cancer Res.
8: 29-34
[Abstract]
[Full Text]
-
Bharadwaj, M., Burrows, S. R., Burrows, J. M., Moss, D. J., Catalina, M., Khanna, R.
(2001). Longitudinal dynamics of antigen-specific CD8+ cytotoxic T lymphocytes following primary Epstein-Barr virus infection. Blood
98: 2588-2589
[Full Text]
-
van Esser, J. W. J., van der Holt, B., Meijer, E., Niesters, H. G. M., Trenschel, R., Thijsen, S. F. T., van Loon, A. M., Frassoni, F., Bacigalupo, A., Schaefer, U. W., Osterhaus, A. D. M. E., Gratama, J. W., Lowenberg, B., Verdonck, L. F., Cornelissen, J. J.
(2001). Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell-depleted SCT. Blood
98: 972-978
[Abstract]
[Full Text]
-
Stevens, S. J. C., Pronk, I., Middeldorp, J. M.
(2001). Toward Standardization of Epstein-Barr Virus DNA Load Monitoring: Unfractionated Whole Blood as Preferred Clinical Specimen. J. Clin. Microbiol.
39: 1211-1216
[Abstract]
[Full Text]
-
Rose, C., Green, M., Webber, S., Ellis, D., Reyes, J., Rowe, D.
(2001). Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment. J. Clin. Microbiol.
39: 1407-1415
[Abstract]
[Full Text]
-
Newstead, C. G.
(2000). Lymphoproliferative disease post-renal transplantation. Nephrol Dial Transplant
15: 1913-1916
[Full Text]
-
(2000). Management of herpes virus infections following transplantation. J Antimicrob Chemother
45: 729-748
[Full Text]
-
Shotelersuk, K., Khorprasert, C., Sakdikul, S., Pornthanakasem, W., Voravud, N., Mutirangura, A.
(2000). Epstein-Barr Virus DNA in Serum/Plasma as a Tumor Marker for Nasopharyngeal Cancer. Clin. Cancer Res.
6: 1046-1051
[Abstract]
[Full Text]
-
Niesters, H. G. M., van Esser, J., Fries, E., Wolthers, K. C., Cornelissen, J., Osterhaus, A. D. M. E.
(2000). Development of a Real-Time Quantitative Assay for Detection of Epstein-Barr Virus. J. Clin. Microbiol.
38: 712-715
[Abstract]
[Full Text]
-
Beck, R., Westdörp, I., Jahn, G., Schäfer, H., Kanz, L., Einsele;, H., Limaye, A. P.
(1999). Detection of Epstein-Barr Virus DNA in Plasma from Patients with Lymphoproliferative Disease after Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplantation. J. Clin. Microbiol.
37: 3430-3431
[Full Text]
Top
Abstract
Introduction
