1. Variable EBV DNA load distributions and heterogeneous EBV mRNA expression patterns in the circulation of solid organ versus stem cell transplant recipients.
- Author
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Greijer AE, Stevens SJ, Verkuijlen SA, Juwana H, Fleig SC, Verschuuren EA, Hepkema BG, Cornelissen JJ, Brooimans RA, Verdonck LF, and Middeldorp JM
- Subjects
- Adolescent, Adult, B-Lymphocytes immunology, B-Lymphocytes virology, Child, DNA, Viral blood, DNA, Viral immunology, Epstein-Barr Virus Infections blood, Epstein-Barr Virus Infections immunology, Epstein-Barr Virus Nuclear Antigens genetics, Epstein-Barr Virus Nuclear Antigens immunology, Female, Herpesvirus 4, Human immunology, Humans, Leukocytes immunology, Leukocytes virology, Lymphoproliferative Disorders blood, Lymphoproliferative Disorders immunology, Lymphoproliferative Disorders virology, Male, Middle Aged, Monocytes immunology, Monocytes virology, RNA, Messenger biosynthesis, RNA, Messenger immunology, RNA, Viral biosynthesis, RNA, Viral immunology, T-Lymphocytes immunology, T-Lymphocytes virology, Viral Load, Viral Matrix Proteins genetics, Viral Matrix Proteins immunology, Viral Proteins genetics, Viral Proteins immunology, Young Adult, DNA, Viral genetics, Epstein-Barr Virus Infections virology, Herpesvirus 4, Human genetics, RNA, Messenger genetics, RNA, Viral genetics, Stem Cell Transplantation
- Abstract
Unlabelled: 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.
- Published
- 2012
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