Persistently High Epstein‐Barr Virus (EBV) Loads in Peripheral Blood Lymphocytes from Patients with Chronic Active EBV Infection

Maeda, Akihiko; Wakiguchi, Hiroshi; Yokoyama, Wakako; Hashimoto, Hiroaki; Tomoda, Takashi; Kurashige, Takanobu

doi:10.1086/314691

Cited by 51 publications

(37 citation statements)

References 14 publications

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“…The viral burden of that sample was estimated to be 4,000 genome copies per 10 4 PBMCs, which was similar to values reported for patients with EBV LPD 41 or chronic active EBV infection. 42 The CTLp level of this patient (340 per 10 6 PBMCs) was similar to that of healthy carriers, and the patient did not show symptoms of either EBV disease. Further amplification revealed the viral genome in 3 other samples, with an estimated viral burden of 1-30 copies (Fig.…”

Section: Ebv Ctlp Frequency and Ebv Burdensupporting

confidence: 53%

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

et al. 2001

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Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of the cancer, we determined levels of EBV-specific CTLp in peripheral blood from NPC patients, long-term survivors of the cancer and healthy subjects. CTLp levels of test subjects varied between 3-3,000/10 6 PBMCs. The plasma EBV burden increased when the CTLp level fell below 150, whereas the EBV burden of PBMCs was not correlated with CTLp level. Compared with healthy carriers, CTLp levels of patients were lower and varied over a wider range, between 3-1,500/10 6 PBMCs. The quantitative immune deficit was probably attributed to the tumor because, first, CTLp in survivors was restored to levels similar to those in healthy carriers after the tumor had been successfully treated. Second, the CTLp level changed as disease progressed, being lower in local disease, increased in locoregional disease and decreased again when the tumor metastasized. Based on these findings, 4 patients with advanced disease were infused with 5 ؋ 10 7 -3 ؋ 10 8 autologous EBV CTLs. The treatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the large tumor bulk. Nevertheless, the treatment regularly increased CTLp levels of patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plasma EBV burden. Taken together, these results provided a rationale to further explore EBV as a target of immune intervention of NPC.

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Section: Ebv Ctlp Frequency and Ebv Burdensupporting

confidence: 53%

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

et al. 2001

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“…Higher values of rates of infections with these viruses are generally obtained when serum or plasma is used as a sample using serological diagnosis, in comparison with estimation by a PCR method. Maeda et al [1999] measured copy numbers of EBV in PBLs from EBVseropositive and EBV-seronegative healthy individuals in Japan by a PCR method and found that the EBV genome was present in 47% of seropositive donors (n ¼ 19) but not in seronegative healthy donors (n ¼ 4). Horvath et al [2000] presented results of a large-scale epidemiologic analysis by PCR showing that CMV and EBV prevalence ratios in PBLs are 11.5% and 8%, respectively, in a normal adult population (n ¼ 85).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of Epstein–Barr virus, cytomegalovirus, and kaposi's sarcoma-associated herpesvirus infections in peripheral blood leukocytes revealed by a multiplex PCR assay

et al. 2006

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A multiplex polymerase chain reaction (PCR) has been developed for the simultaneous detection of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Kaposi's sarcoma-associated herpesvirus (KSHV) in a clinical sample. Primers of multiplex PCR were designed to amplify specific regions of the EBV EBNA1, CMV IE2, and KSHV LANA genes. This multiplex PCR assay was found to have detection sensitivities of 1-10 copies of purified viral DNA cloned into the plasmid. To assess diagnostic and pre-clinical applications with this method, we utilized KSHV-positive primary effusion lymphoma (PEL) cells, EBV-positive Burkitt's lymphoma cells, CMV-infected fibroblast cells, and clinically prepared peripheral blood leukocytes (PBLs) that had been infected with viruses. We found that this multiplex PCR assay has high sensitivity and specificity for simultaneous detection of EBV, CMV, and KSHV genomes in a single amplification from a clinical material. Using this multiplex PCR assay, we investigated the prevalence of EBV, CMV, and KSHV in PBL samples from normal Japanese randomly selected. KSHV, EBV, and CMV genomes were detected in samples from 2 (0.2%), 377 (39.5%), and 27 (2.8%) of the 953 blood donors, respectively. Interestingly, both EBV and CMV genomes were detected in samples from all KSHV-positive donors.

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“…Since EBV may replicate without causing apparent harm, it is important to be able to distinguish asymptomatic infection from impending or established EBV disease. Because of this, quantitative methods for measuring EBV are now widely utilized for the diagnosis, monitoring, and treatment of EBVrelated diseases, particularly in the case of posttransplant lymphoproliferative disorder (1,9). In addition, studies have indicated that preemptive treatment for EBV and reduction in immunosuppressive therapy can reduce the incidence of posttransplant lymphoproliferative disorder in immunocompromised patients (1,7).…”

Section: Epstein-barr Virus (Ebv)mentioning

confidence: 99%

Multicenter Comparison of Different Real-Time PCR Assays for Quantitative Detection of Epstein-Barr Virus

Hayden¹,

et al. 2008

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Quantification of Epstein-Barr virus (EBV) in peripheral blood is important for the diagnosis and management of serious EBV diseases, including posttransplant lymphoproliferative disorder. A variety of PCRbased methods are currently in use; however, there is little information on their comparability. This study assessed the relative performance of different quantitative assays. A multicenter comparative study was performed at eight sites using three panels consisting of serial dilutions of quantified EBV DNA and extracts from a total of 19 whole-blood specimens. Samples were distributed and tested blindly. Instrumentation, probe chemistries, amplification targets, and other test-related aspects varied considerably between laboratories. Each laboratory's calibration curve indicated strong evidence of a consistent log-linear relationship between viral load and cycle threshold, suggesting that intralaboratory tracking of a given patient would yield similar relative quantitative trends among the participating test sites. There was strong concordance among laboratories with respect to qualitative test results; however, marked quantitative discordance was seen. For most samples, the across-laboratory interquartile range of the reported viral load (in copies/l) was roughly 0.6 log-units, and for one sample the overall range was approximately 4.2 log-units. While intralaboratory tracking of patients may yield similar results, these data indicate a need for caution when attempting to compare clinical results obtained at different institutions and suggest the potential value to be gained by more standardized testing methodology.

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Persistently High Epstein‐Barr Virus (EBV) Loads in Peripheral Blood Lymphocytes from Patients with Chronic Active EBV Infection

Cited by 51 publications

References 14 publications

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

Epidemiology of Epstein–Barr virus, cytomegalovirus, and kaposi's sarcoma-associated herpesvirus infections in peripheral blood leukocytes revealed by a multiplex PCR assay

Multicenter Comparison of Different Real-Time PCR Assays for Quantitative Detection of Epstein-Barr Virus

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