Predictive Value of Epstein‐Barr Virus Genome Copy Number and<i>BZLF1</i>Expression in Blood Lymphocytes of Transplant Recipients at Risk for Lymphoproliferative Disease

Vajro, Pietro; Lucariello, S.; Migliaro, Fiorella; Sokal, Étienne; Gridelli, Bruno; Vegnente, Angela; Iorio, Raffaele; Smets, Françoise; Quinto, Ileana; Scala, Giuseppe

doi:10.1086/315495

Cited by 41 publications

(27 citation statements)

References 14 publications

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“…This is in accordance with our observations of transplant patients (30) Contrary to data from previous studies (9,19,27), we did not manage to amplify BZLF1-specific mRNA in samples from our healthy cohort. This negative result might be due to the fact that those previous studies analyzed BZLF1 mRNA expression partly in solid-organ transplant recipients (9,27) and patients with infectious mononucleosis (19). However, it is noteworthy that two other studies investigating transplant recipients also did not find ZEBRA mRNA even by nested RT-PCR (21,35).…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…Thus, some authors have used serum PCR to evaluate EBV replication. 3,42 In our series, a low correlation is observed between PCR in blood and replication analysis in involved organs, similarly to what is observed in other virus that replicates in tissues. 43,44 In the latent stage, EBV DNA exists as a closed circular episome, replicates once, and only once during S phase, and is equally distributed into daughter cells.…”

Section: Discussionsupporting

confidence: 83%

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

et al. 2014

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Post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. They represent a spectrum of mostly EBV-driven lymphoplasmacytic proliferations. While the oncogenic effect of EBV is related to latent infection, lytic infection also has a role in lymphomagenesis. In vitro, EBV replication is linked to plasma cell differentiation and XBP1 activation, although this phenomenon has never been addressed in vivo. We analyzed for the first time latent and lytic intratumoral EBV infection in a series of 35 adult patients with a diagnosis of post-transplant lymphoproliferative disorder (26M/9F, median age 54 years). A complete EBV study was performed including the analysis of the latent EBER, latent membrane protein-11, and EBV nuclear antigens as well as the immediate-early BZLF1/ ZEBRA and early BMRF1/EADE31 lytic genes. XBP1 activation was assessed by nuclear protein expression. EBV infection was observed in 28 (80%) cases being latency II and III the most frequently observed 22 (79%). Intratumoral EBV replication was detected in 17 (60%) cases. Among these, XBP1 activation was observed in 11/12 evaluable cases associated with strong cytoplasmic immunoglobulin expression consistent with plasma cell differentiation. Intriguingly, the combination of latency III infection and EBV replication identified a high-risk subgroup of patients with significantly shorter survival (overall survival at 1 year 18% vs 48%) and early-onset (median of 7 vs 26 months) post-transplant lymphoproliferative disorder. Moreover, these patients appear to be more heavily immunosuppressed, so they exhibit lower rates of rejection and graft vs host disease but higher rates of cytomegalovirus reactivation. In conclusion, EBV replication is associated with plasma cell

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“…Before the occurrence of symptomatic disease there is a period of approximately 2 to 6 weeks when the rising EBV load can be detected by PCR. PTLD is associated with a very high EBV load circulating in the peripheral blood: Ͼ1,000 copies of EBV genomes/10 5 PBLs in most cases and greater than 200 copies/10 5 PBLs with rare exceptions (4,11,12,19,21,23,29,34,36,38,39,46). Resolution of EBV infection in pediatric solid-organ transplant recipients is often accompanied by a persistent high circulating EBV load 2 to 3 orders of magnitude higher than the viral load observed in latently infected immunocompetent individuals.…”

Section: Peripheral Blood Lymphocytes) Fish Analysis Revealed That Tmentioning

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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Predictive Value of Epstein‐Barr Virus Genome Copy Number andBZLF1Expression in Blood Lymphocytes of Transplant Recipients at Risk for Lymphoproliferative Disease

Cited by 41 publications

References 14 publications

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

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

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

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

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