Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients

Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular...

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Main Authors: A. E. Greijer, S. J. Stevens, S. A. Verkuijlen, H. Juwana, S. C. Fleig, E. A. Verschuuren, B. G. Hepkema, J. J. Cornelissen, R. A. Brooimans, L. F. Verdonck, J. M. Middeldorp
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/543085
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author A. E. Greijer
S. J. Stevens
S. A. Verkuijlen
H. Juwana
S. C. Fleig
E. A. Verschuuren
B. G. Hepkema
J. J. Cornelissen
R. A. Brooimans
L. F. Verdonck
J. M. Middeldorp
author_facet A. E. Greijer
S. J. Stevens
S. A. Verkuijlen
H. Juwana
S. C. Fleig
E. A. Verschuuren
B. G. Hepkema
J. J. Cornelissen
R. A. Brooimans
L. F. Verdonck
J. M. Middeldorp
author_sort A. E. Greijer
collection DOAJ
description Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n=5), solid organ transplant recipients (SOT; n=15), and SOT having chronic elevated EBV-DNA load (n=12). In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8) or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. Conclusion: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA.
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spelling doaj-art-12c2b2ea59524b99b7fc650f42e40e2d2025-08-20T02:02:11ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/543085543085Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant RecipientsA. E. Greijer0S. J. Stevens1S. A. Verkuijlen2H. Juwana3S. C. Fleig4E. A. Verschuuren5B. G. Hepkema6J. J. Cornelissen7R. A. Brooimans8L. F. Verdonck9J. M. Middeldorp10Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Clinical Genetics, Academic Hospital Maastricht, 6202 AZ Maastricht, The NetherlandsDepartment of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsDepartment of Pulmonary Diseases, University Medical Centre Groningen, 9700 RB Groningen, The NetherlandsDepartment of Laboratory Medicine, University Medical Centre Groningen, 9700 RB Groningen, The NetherlandsDepartment of Hematology, University Medical Center Rotterdam, 3000 CA Rotterdam, The NetherlandsDepartment of Hematology, University Medical Center Rotterdam, 3000 CA Rotterdam, The NetherlandsDepartment of Hematology, University Medical Center, 3508 GA Utrecht, The NetherlandsDepartment of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsEpstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n=5), solid organ transplant recipients (SOT; n=15), and SOT having chronic elevated EBV-DNA load (n=12). In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8) or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. Conclusion: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA.http://dx.doi.org/10.1155/2012/543085
spellingShingle A. E. Greijer
S. J. Stevens
S. A. Verkuijlen
H. Juwana
S. C. Fleig
E. A. Verschuuren
B. G. Hepkema
J. J. Cornelissen
R. A. Brooimans
L. F. Verdonck
J. M. Middeldorp
Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
Clinical and Developmental Immunology
title Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
title_full Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
title_fullStr Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
title_full_unstemmed Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
title_short Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients
title_sort variable ebv dna load distributions and heterogeneous ebv mrna expression patterns in the circulation of solid organ versus stem cell transplant recipients
url http://dx.doi.org/10.1155/2012/543085
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