Epstein‐Barr Virus (EBV) Early‐Antigen Serologic Testing in Conjunction with Peripheral Blood EBV DNA Load as a Marker for Risk of Posttransplantation Lymphoproliferative Disease

2003 ◽  
Vol 188 (12) ◽  
pp. 1853-1864 ◽  
Author(s):  
Linda Carpentier ◽  
Bruce Tapiero ◽  
Fernando Alvarez ◽  
Carole Viau ◽  
Caroline Alfieri
Keyword(s):  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Early Antigen ◽  
Barr Virus ◽  
Serologic Testing ◽  
Ebv Dna ◽  
Epstein Barr

scholarly journals Epstein‐Barr Virus (EBV) Early‐Antigen Antibodies and EBV DNA Load in Blood, in Posttransplantation Lymphoproliferative Disease

2004 ◽  
Vol 190 (8) ◽  
pp. 1524-1525 ◽  
Author(s):  
Marianne Leruez‐Ville ◽  
Cécile Talbotec ◽  
Frank Iserin ◽  
Rémi Salomon ◽  
Florence Lacaille ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Early Antigen ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1165-1171 ◽  
Author(s):  
Servi J. C. Stevens ◽  
Erik A. M. Verschuuren ◽  
Inge Pronk ◽  
Wim van der Bij ◽  
Martin C. Harmsen ◽  
...  
Keyword(s):  
Whole Blood ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Serum Samples ◽  
Barr Virus ◽  
Load Monitoring ◽  
Risk Patients ◽  
Posttransplant Lymphoproliferative Disease ◽  
Ebv Dna ◽  
Epstein Barr

Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)–associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P < .0001) despite heavy immune suppression and cytomegalovirus (CMV)-related disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV+ cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection.

scholarly journals Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Antoine Chaillon ◽  
Masato Nakazawa ◽  
Stephen A. Rawlings ◽  
Genevieve Curtin ◽  
Gemma Caballero ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Molecular Diversity ◽  
Viral Shedding ◽  
Barr Virus ◽  
Hiv Dna ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Over Time ◽  
Dna Reservoir

ABSTRACT Cytomegalovirus (CMV) almost universally infects persons with HIV (PWH), and it is a driver of persistent inflammation and HIV persistence. The mechanisms underlying the association between CMV (and possibly other herpesviruses) and HIV persistence are unclear. Serially collected blood samples were obtained from men who have sex with men (MSM) who started antiretroviral therapy (ART) within 1 year of their estimated date of HIV infection (EDI). Total CMV and Epstein-Barr virus (EBV) DNA were quantified in peripheral blood mononuclear cells by droplet digital PCR (ddPCR). Deep sequencing of the HIV DNA partial env gene was performed, and the dynamics of viral diversity over time were analyzed in relation to CMV and EBV shedding status. In total, 37 MSM PWH were included and followed for a median of 23 months (IQR, 22 to 28). Participants started ART within a median of 3.1 months (IQR, 1.5 to 6.5) after EDI and remained virally suppressed thereafter. A total of 18 participants (48.6%) were classified as high EBV shedders, while 19 (51.4%) were classified as CMV shedders. In longitudinal analyses, normalized molecular diversity levels tended to increase over time among participants with detectable CMV and high EBV DNA (0.03 ± 0.02, P = 0.08), while they significantly declined among participants with no/low viral shedding (−0.04 ± 0.02, P = 0.047, interaction P < 0.01). Subclinical CMV and EBV shedding could contribute to the dynamics of the HIV DNA reservoir during suppressive ART. Whether persistent CMV/EBV replication could be targeted as a strategy to reduce the size of the latent HIV reservoir is an avenue that should be explored. IMPORTANCE As part of this study, we evaluated the molecular characteristics of the HIV DNA reservoir over time during antiretroviral treatment (ART) in relation to those of other chronic viral infections (i.e., cytomegalovirus [CMV] and Epstein-Barr virus [EBV]). We demonstrated that the presence of CMV and high-level EBV DNA in peripheral blood cells was associated with changes in HIV DNA molecular diversity. Specifically, HIV DNA molecular diversity increased over time among participants with detectable CMV and high-level EBV DNA, while it significantly declined among participants with no/low viral shedding. Although the current study design does not allow causality to be inferred, it does support the theory that persistent CMV and EBV shedding could contribute to the dynamics of the HIV DNA reservoir during suppressive ART, even when ART is initiated during the earliest phases of HIV infection.

Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 807-814 ◽  
Author(s):  
Åsa Gustafsson ◽  
Victor Levitsky ◽  
Jie-Zhi Zou ◽  
Teresa Frisan ◽  
Tina Dalianis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Blood Levels ◽  
Moderate Increase ◽  
Allogeneic Bone ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

A semiquantitative polymerase chain reaction assay was used to monitor the blood levels of Epstein-Barr virus (EBV)-DNA in 9 patients receiving allogeneic bone marrow transplants (BMT). Four of 5 recipients of HLA-mismatched T-cell–depleted grafts showed a 4- to 5-log increase of EBV-DNA within 1 to 3 months after BMT. Administration of 2 to 4 infusions of 107 EBV-specific cytotoxic T-lymphocytes (CTLs)/m2 starting from the time of maximal virus load resulted in a 2- to 3-log decrease of virus titers in 3 patients. One patient, who received a T-cell culture lacking a major EBV-specific component, progressed to fatal EBV-positive lymphoma. Administration of EBV-CTLs before the onset of the EBV-DNA peak resulted in stabilization of the virus titers within 2 to 3 logs above the normal levels in the fifth patient. A moderate increase of virus titers was also detected in 3 of 4 patients receiving unmanipulated HLA-matched grafts, whereas 1 patient with Wiskott-Aldrich syndrome reached a 5-log increase of EBV-DNA load within 70 days after BMT. Our results suggest that a rapid increase of circulating EBV-DNA occurs in the absence of EBV-specific T-cell precursors or in the presence of congenital immune defects that prevent the reestablishment of virus-specific immunity. Prophylactic administration of EBV-CTLs early after BMT appears to provide the most effective protection against the development of EBV-associated lymphoproliferative disease.

scholarly journals 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 ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2715-2722 ◽  
Author(s):  
A Savoie ◽  
C Perpete ◽  
L Carpentier ◽  
J Joncas ◽  
C Alfieri
Keyword(s):  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Mononuclear Cells ◽  
Polymerase Chain Reaction Amplification ◽  
Lymphoproliferative Disease ◽  
Lymphocyte Culture ◽  
Barr Virus ◽  
Transplant Patients ◽  
Infected Cells ◽  
Epstein Barr

Abstract The Epstein-Barr virus (EBV) is known to cause posttransplant lymphoproliferative disease (PTLD) in immunosuppressed transplant patients. The results of this pilot study showed that all EBV- patients pretransplant experienced primary EBV infection within the first 3 months after transplant surgery. Virtually all of these patients had a higher burden of EBV-infected cells in their peripheral blood (PB) after infection by EBV than did the EBV+ pretransplant group when tested at the same intervals posttransplant. Salivary EBV titers also increased in most patients, but the difference between the two groups was statistically significant only at 12 months, whereupon EBV+ patients showed higher titers compared with EBV- (alpha < 0.053). Also, polymerase chain reaction amplification followed by Southern blotting was performed to detect EBV sequences in PB mononuclear cells. This technique allowed confirmation of the blood culture results and constituted a faster alternative compared with the culture assay. The highest increase in the number of EBV-infected lymphocytes at 3 months posttransplant obtained from PB was seen in a patient who developed fatal PTLD and in another with protracted infectious mononucleosis. Thus, the number of EBV-infected cells in PB was found to correlate positively with risk of development of PTLD at 3 months posttransplant in our group of pediatric transplant patients. This study showed that quantitative lymphocyte culture of PB was an accurate index of immunosuppression and a reliable method for assessing the risk of PTLD development.

scholarly journals The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma

2011 ◽  
Vol 17 (9) ◽  
pp. 2885-2892 ◽  
Author(s):  
Stefan Hohaus ◽  
Rosaria Santangelo ◽  
Manuela Giachelia ◽  
Barbara Vannata ◽  
Giuseppina Massini ◽  
...  
Keyword(s):  
Viral Load ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Clinical Characteristics ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

scholarly journals Prevention of Epstein-Barr virus–lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4364-4369 ◽  
Author(s):  
Joost W. J. van Esser ◽  
Hubert G. M. Niesters ◽  
Bronno van der Holt ◽  
Ellen Meijer ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
High Risk ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Viral Reactivation ◽  
Preemptive Therapy ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Risk Patients ◽  
Ebv Dna ◽  
Epstein Barr

Recipients of a partially T-cell–depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV–lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite pre-emptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% ± 9% versus 49% ± 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% ± 10%, respectively) (P = .04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD.

scholarly journals Chronic active Epstein–Barr virus infection manifesting as coronary artery aneurysm and uveitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Haijuan Xiao ◽  
Bing Hu ◽  
Rongmu Luo ◽  
Huili Hu ◽  
Junmei Zhang ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Coronary Artery Aneurysm ◽  
Artery Aneurysm ◽  
Epstein Barr Virus Infection ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Background Chronic active Epstein–Barr virus (CAEBV) infection is a type of lymphoproliferative disorder characterized by chronic or recurrent infectious mononucleosis (IM)-like symptoms, which can have less-frequent clinical presentations. The prognosis of CAEBV is poor, and hematopoietic stem cell transplantation (HSCT) has been shown to be the only potentially effective treatment. In this article, we present a special CAEBV case of a patient who had no typical IM-like symptoms at the early stage, but manifested with severe and progressive coronary artery aneurysm (CAA), abdominal aortic lesions, and severe uveitis. These manifestations were uncommon features and could only be blocked by HSCT. Case presentation A 4-year-old girl with no special medical history complained of decreased vision for 10 months and cough after physical activities for three months. The blurred vision grew rapidly worse within one month, until only light perception remained. She was diagnosed with uveitis and cataract, and received prednisone and ciclosporin A treatment. However, her vision did not improve. Physical examination showed slight hepatosplenomegaly. Ultrasonic cardiogram showed bilateral CAA (5.0 mm and 5.7 mm for inner diameters), and abdominal CT scan revealed a thickened aortic wall, as well as stenosis and dilation of the segmental abdominal aorta. Other significant findings were increased EBV-DNA (3.29 × 104 copies/mL) from peripheral blood, positive EBV antibodies (EBV-CA-IgG, EBV-EA-IgA, and EBV-NA-IgG), and positive EBV-encoded small RNAs found by bone marrow biopsy. Based on her clinical manifestations and evidence for EBV infection, we diagnosed CAEBV. She received allogeneic HSCT, and the cataract operation was performed after HSCT. EBV-DNA could not be detected in peripheral blood after HSCT. Her CAAs did not progress, and uveitis was well controlled. Her vision recovered gradually over the 3 years after HSCT. Conclusions We present a rare CAEBV case of a patient who suffered from uncommon and severe cardiovascular and ocular involvement that was relieved by HSCT. Therefore, early recognition and diagnosis of CAEBV are of vital importance to improve its prognosis. In summary, this atypical CAEBV case could help us recognize similar cases more easily, make the right diagnosis as early as possible, and deliver proper and timely treatment.

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