Coincidence of Epstein-Barr Virus Reactivation, Cytomegalovirus Infection, and Rejection Episodes in Renal Transplant Recipients

Hornef, Mathias W.; Bein, Gregor; Fricke, Lutz; Steinhoff, Jürgen; Wagner, Hans-J; Hinderer, Walter; Sonneborn, H.‐H.; Kirchner, Holger

doi:10.1097/00007890-199509000-00013

Cited by 59 publications

(42 citation statements)

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“…On the other hand several PTLD patients had no CMV-related problems. These findings are in contrast to data published by Hornef et al, 31 who found coincidence of symptomatic CMV infection, rejection episodes, and serologic signs of EBV reactivation in renal transplantation recipients. In patient no.…”

Section: Discussioncontrasting

confidence: 99%

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

Stevens

Verschuuren

Pronk

et al. 2001

Blood

304

216

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Section: Discussioncontrasting

confidence: 99%

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

Stevens

Verschuuren

Pronk

et al. 2001

Blood

304

216

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“…A few clinical studies have investigated whether there is an association between CMV and Epstein-Barr virus (EBV) reactivation in the blood compartment of immunosuppressed patients. While some authors (24,21) have found that reactivation of each virus occurred independently, others (9,11) have shown an association between CMV infection and the serologic profile of EBV reactivation. In vitro studies have shown as well that there might be an association between CMV and EBV (2).…”

mentioning

confidence: 99%

Relationship between Cytomegalovirus DNA Load in Epithelial Lining Fluid and Plasma of Lung Transplant Recipients and Analysis of Coinfection with Epstein-Barr Virus and Human Herpesvirus 6 in the Lung Compartment

et al. 2007

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Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). The aim of the present study was to elucidate the relationship between the CMV DNA load in the lung compartment and that in plasma. For CMV load determination, the level of CMV DNA in plasma and bronchoalveolar lavage (BAL) samples was measured in a total of 97 paired BAL and plasma samples obtained from 25 LTRs. The original virus concentration in the epithelial lining fluid (ELF) was calculated from the BAL samples by correcting for dilution using the urea dilution method. In addition, the load of Epstein-Barr virus (EBV) and that of human herpesvirus 6 (HHV-6) DNA also were determined in BAL samples, recalculated for their concentrations in the ELF, and compared with the CMV DNA load. CMV DNA was found more frequently and at significantly higher levels in the lung compartment than in plasma (P < 0.001, Wilcoxon test), and the CMV load in the ELF was associated with symptomatic CMV disease. EBV and HHV-6 were detected in 43.6% and 21.7% of the ELF samples, respectively. A statistically significant association was found between the CMV and EBV DNA loads in the ELF (P < 0.001; Spearman's rho ‫؍‬ 0.651). Thus, in LTRs, determination of the CMV DNA load in the lung compartment may be advantageous compared to monitoring only viremia. The significant relationship between EBV and CMV DNA loads in the ELF of LTRs and its clinical impact require further investigation.Herpesvirus infections are a considerable burden and pose a challenge to the management of organ transplant recipients (16). Among herpesvirus infections, cytomegalovirus (CMV) infection is one of the most severe complications in organ transplant patients, and lung transplant recipients (LTRs) are at particularly high risk of developing CMV infection and disease (23). CMV detection in bronchoalveolar lavage (BAL) samples has been described as an earlier marker of virus replication in the lung than detection using PCR analysis of blood (4). However, CMV DNA quantitation from BAL samples has not been established as a routine predictive marker because a substantial overlap between virus loads in symptomatic and asymptomatic patients has been shown (4). This inability to discriminate symptomatic from asymptomatic LTRs by CMV DNA quantitation with BAL samples may be explained by the variability of the amount of epithelial lining fluid (ELF) which is recovered from the surface of the lung by BAL sampling. We have recently shown that in order to achieve an exact quantification of the CMV load in the lung compartment, corrections have to be made to account for the dilution of the original ELF containing the virus in the final BAL sample. Using this approach, we have found that the virus level in the lung compartment is clearly associated with CMV disease (27).The number of studies in which interactions between herpesviruses in transplant patients have been investigated is limited, and data on viral coinfection in the lung compartment are especially rare. A...

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“…Under healthy conditions, this system is well balanced and almost no specific symptoms indicate these events, but in patients under immunosuppression, e.g., after solid organ or stem cell transplantation or with an acquired T-cell immunodeficiency like human immunodeficiency virus infection, viral reactivation is suspected to cause severe complications. Several studies have connected lytic activity and reactivation with rejection episodes in transplant recipients (3,8), posttransplant lymphoproliferative disorder (PTLD) (20,23,33), and clinical disease activity in patients with multiple sclerosis (34). Immunosuppression seems to trigger not only reactivation but also physically or psychologically challenging situations that result in diminished cell-mediated immunity (6,14,18).…”

mentioning

confidence: 99%

“…Until now, EBV reactivation has been diagnosed only by means of serology (8,16,24), by determination of transformational activity in throat washings (20,36), or by EBV DNA analysis of saliva samples (10,16,18). Serology, however, re-flects reactivation only retrospectively and does not represent the actual event.…”

mentioning

confidence: 99%

Molecular Parameters for Precise Diagnosis of Asymptomatic Epstein-Barr Virus Reactivation in Healthy Carriers

Maurmann¹,

Fricke²,

Wagner³

et al. 2003

J Clin Microbiol

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Asymptomatic Epstein-Barr virus (EBV) reactivations periodically occur in oral mucosa-associated lymphoid tissues. Until now, EBV reactivation has been diagnosed by serologic profiles that suggest virus replication. Serologic responses, however, are delayed and do not necessarily indicate ongoing replicative activity. The aim of the present study was to establish in healthy carriers parameters for a molecular diagnosis of reactivated EBV infection. Recent studies emphasized the association of an increase in peripheral-B-cell viral load with replicative activity at remote sites. Therefore, real-time PCR was used to quantitate EBV genomes in the peripheral blood mononuclear cells (PBMC) (viral load) and plasma samples (viremia) of 22 healthy EBV-seropositive blood donors over a period of 15 months. Furthermore, transcription of the immediate-early gene encoding BZLF1 was investigated in the PBMC of all volunteers. Serology suggested reactivation in nine donors, of whom all but one showed at least once a significant increase in viral load. Another five individuals also exhibited significant changes in viral load but no serologic response. Of the 13 volunteers with significant increases in viral load, 6 had a period of viremia accompanying the rise in viral load. A stable viral load without viremia and negative serology was seen in eight adults. BZLF1 mRNA was undetectable throughout. We conclude that for healthy subjects serology underestimates the frequency of asymptomatic EBV reactivations. Prospective examination of peripheral viral load and viremia is suitable for the exact diagnosis of EBV reactivation, which might be of advantage for immunocompromised patients in whom EBV reactivations are considerably harmful.

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Coincidence of Epstein-Barr Virus Reactivation, Cytomegalovirus Infection, and Rejection Episodes in Renal Transplant Recipients

Cited by 59 publications

References 0 publications

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

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

Relationship between Cytomegalovirus DNA Load in Epithelial Lining Fluid and Plasma of Lung Transplant Recipients and Analysis of Coinfection with Epstein-Barr Virus and Human Herpesvirus 6 in the Lung Compartment

Molecular Parameters for Precise Diagnosis of Asymptomatic Epstein-Barr Virus Reactivation in Healthy Carriers

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