Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment

Rose, Camille; Green, Michael; Webber, Steven A.; Ellis, Demetrius; Reyes, Jared; Rowe, David

doi:10.1128/jcm.39.4.1407-1415.2001

Cited by 34 publications

(22 citation statements)

References 23 publications

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“…The elevated viral DNA loads seen in these patients appeared to be associated with latent virus because (i) no viral DNA was detected in the plasma fraction, (ii) immortalization or lytic replication genes were not expressed, and (iii) the load was restricted to the memory B-cell compartment (30,35). Beyond the high loads, the only distinction between immunocompromised and healthy individuals was the expression of LMP1 RNA in all the carriers with loads greater than 200 copies/10 5 lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization

Rose

Green

Webber³

et al. 2002

J Clin Microbiol

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Section: Discussionmentioning

confidence: 99%

Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization

Rose

Green

Webber³

et al. 2002

J Clin Microbiol

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“…This result has been confirmed in two recently published studies which demonstrated the lack of use of plasma or serum VL measurements even with quantitative PCR or real time PCR. 42,45 The post-transplantation kinetics of EBV DNA levels show undetectable viral DNA levels during the first month after transplantation, probably because of the limited number of circulating B lymphocytes. Significant fluctuations of post-transplantation EBV-VL were seen thereafter in HLA non-genoidentical graft recipients as opposed to HLA genoidentical graft recipients who showed no major posttransplantation variation.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Bueltzingsloewen

Morand

Buisson

et al. 2002

Bone Marrow Transplant

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Summary:EBV viral load (EBV-VL) in PBMC was prospectively determined by semi-quantitative PCR in 85 stem cell transplants (40 genoidentical, 45 non-genoidentical) in order to characterize the kinetics of EBV-VL and to assess the ability of this measure to predict the development of EBV-induced lymphoproliferative disease (EBV-LPD). PCR was performed prior to and after transplantation. An EBV-VL Ͼ300 copies/ g DNA was chosen as the threshold for risk of developing an EBV-LPD. Two hundred and fifty-eight EBV-VL measures were evaluable. Five patients (5.9%) developed an EBV-LPD. All had an elevated EBV DNA peak level before EBV-LPD. Fifteen out of 80 recipients (18.7%) without EBV-LPD had EBV levels over 300 copies/ g DNA at least once during the follow-up. Overall, the manifestation of at least one EBV-VL over 300 copies/ g DNA during the entire follow-up demonstrated a sensitivity, specificity, positive and negative predictive value for the diagnosis of EBV-LPD of 100%, 81%, 25% and 100%, respectively. In patients without EBV-LPD, HLA incompatibility, grade уII acute GVHD and use of an unmanipulated graft were significantly associated with an EBV-VL Ͼ300 copies/ g DNA. This strategy appears sensitive for the diagnosis of EBV-LPD but its positive predictive value has to be improved in order to guide pre-emptive therapy.

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“…Our laboratory and others (31,33,34) have shown previously that patients treated with immunosuppressive agents following organ transplant have high frequencies of EBV-infected cells in their blood. SLE patients are also treated with immunosuppressive drugs, albeit with fewer agents and at lower doses than patients who have received organ transplants.…”

Section: Treatment Of Sle Patients With Immunosuppressive Agents Doesmentioning

confidence: 99%

“…A hallmark of EBV infection in healthy individuals is the restriction of the virus to the IgD Ϫ population of memory B cells in the blood (24,34,42). The appearance of EBV in peripheral blood naive B cell would represent a profound deregulation of persistent infection.…”

Section: The Infected Cells In the Blood Of Patients With Sle Are Memmentioning

confidence: 99%

EBV and Systemic Lupus Erythematosus: A New Perspective

Gross

Hochberg²,

Rand

et al. 2005

The Journal of Immunology

195

178

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We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.

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Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment

Cited by 34 publications

References 23 publications

Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization

Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization

A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

EBV and Systemic Lupus Erythematosus: A New Perspective

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