Epstein‐Barr Virus Gene Expression in the Peripheral Blood of Transplant Recipients with Persistent Circulating Virus Loads

Qu, Lirong; Green, Michael; Webber, Steven A.; Reyes, Jared; Ellis, Demetrius; Rowe, David

doi:10.1086/315828

Cited by 87 publications

(72 citation statements)

References 33 publications

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“…This is based on studies of immunosuppressed organ transplant recipients who have high numbers of EBV-infected cells in the blood (31,33,(45)(46)(47) and are at risk for EBV lymphoproliferative diseases (48). In this study, we have shown that patients with SLE also have elevated frequencies of infected cells in the blood, similar to those seen in immunosuppressed organ transplant recipients (31).…”

Section: Discussionmentioning

confidence: 52%

“…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: 90%

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EBV and Systemic Lupus Erythematosus: A New Perspective

Gross

Hochberg²,

Rand

et al. 2005

The Journal of Immunology

202

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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Section: Discussionmentioning

confidence: 52%

Section: Treatment Of Sle Patients With Immunosuppressive Agents Doesmentioning

confidence: 90%

EBV and Systemic Lupus Erythematosus: A New Perspective

Gross

Hochberg²,

Rand

et al. 2005

The Journal of Immunology

202

178

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“…Therefore, the risk of developing PTLD continues for life, although early PTLD (in the first year after transplantation) occurs in cases of primary EBV infection [76]. On the otherhand asymptomatic EBV reactivation with high viral load is observed during the extended post-transplant follow-up [77]. The predictive value of the EBV load in solid organ transplantation is less clear, because some recipients have high EBV loads and remain stable for months or years without developing PTLD [78,79].…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

“…Additional information on viral gene expression would provide a better assessment of each patient's condition [39]. Qu et al examined the expression of EBV-associated genes in solid organ transplant recipients and found that persistent low-load carriers expressed only LMP-2, whereas high-load carriers expressed both LMP-1and LMP-2 [77]. They used qualitative reversetranscription PCR to detect EBV-associated genes.…”

Section: Future Perspectivesmentioning

confidence: 99%

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

137

142

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Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

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“…In addition, the determination of quantitative EBV genomic levels in peripheral blood may provide presumptive evidence for EBV involvement because EBVrelated complications are often associated with an increase in the circulating virus level. [13][14][15][16][17] It must be stressed that sensitivity and specificity of this assay have not yet been determined.…”

mentioning

confidence: 99%

Posttransplant lymphoproliferative disorder and tonsillectomy in a pediatric liver transplant population

Nalesnik¹

2001

Liver Transplantation

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CommentsPosttransplant lymphoproliferative disorders (PTLDs) represent a syndrome of abnormal lymphoid growths, most commonly of B-lymphocyte origin and associated with Epstein-Barr virus (EBV). High levels of immunosuppression and primary EBV infection are 2 factors that predispose to the development of this disease. In part because of this, the pediatric as opposed to the adult allograft population is at especially increased risk for PTLD. 1,2 Broughton et al 3 report on a retrospective review of posttransplantation tonsillectomies in their pediatric liver transplant population, with the intent of evaluating the utility of this intervention for the diagnosis of PTLD. In their series, tonsillectomies were performed in 4.7% of patients over a 15-year period. The article raises several interesting points.First, it is stated that 5 of the 13 specimens (39%) showed evidence of an EBV-related disorder. However, it is noted that 5 tonsillectomies in this series were performed before the routine application of the sensitive in situ hybridization test for Epstein-Barr early RNA to pathological specimens. This technique is capable of detecting EBV at the single-cell level. An additional 3 specimens in this series were not assayed with this techinque. Therefore, 5 of the 13 specimens were tested for EBV, and the virus was detected in 4 of these 5 specimens (80%). Pretransplantation EBV serostatus is not provided, but an earlier series by Ho et al 1 showed posttransplantation primary EBV infection in 77% of pediatric liver transplant recipients who were seronegative at time of transplantation, with 48% of previously seropositive patients showing evidence of reactivation infection. Thus, the 39% frequency rate of EBV presence in resected tonsillar hypertrophy must be considered a lower limit, with more sensitive procedures placing the figure closer to 80%.Second, the intervals between transplantation and tonsillectomy provide an interesting perspective. The patient with the longest interval from transplantation to tonsillectomy (12 years) was found to have tonsillar hyperplasia. Conversely, the single patient with tonsillar lymphoma developed symptoms 3 months after liver transplantation. This contradicts 2 common misconceptions: (1) all tonsillar PTLDs are simply manifestations of infectious mononucleosis, and (2) late-arising lesions are invariably true lymphomas. The importance of biopsy diagnosis for clinical guidance cannot be overemphasized.Third, the patient with tonsillar lymphoma was found to have an abdominal mass that also represented lymphomatous PTLD, highlighting that PTLD may involve more than 1 site. In some cases, this may simply reflect generalized lymphadenopathy seen as part of a systemic EBV infection. In other cases, the disease may present as multiple independent clonal proliferations. Finally, some cases may represent high-grade lymphomas with metastatic disease. In one series, 4 35% of combined pediatric and adult patients with PTLD were found to have Ann Arbor stage I disease, 15% had stage II, 23...

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Epstein‐Barr Virus Gene Expression in the Peripheral Blood of Transplant Recipients with Persistent Circulating Virus Loads

Cited by 87 publications

References 33 publications

EBV and Systemic Lupus Erythematosus: A New Perspective

EBV and Systemic Lupus Erythematosus: A New Perspective

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Posttransplant lymphoproliferative disorder and tonsillectomy in a pediatric liver transplant population

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