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 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.


CONCLUSIONS
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.
Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
A E
AE
Greijer
S J
SJ
Stevens
S A
SA
Verkuijlen
H
H
Juwana
S C
SC
Fleig
E A
EA
Verschuuren
B G
BG
Hepkema
J J
JJ
Cornelissen
R A
RA
Brooimans
L F
LF
Verdonck
J M
JM
Middeldorp
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002648:Child; D004279:DNA, Viral / Q000097:blood / Q000235:genetics* / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1