scholarly journals The Role of Epstein-Barr Virus in Adults With Bronchiectasis: A Prospective Cohort Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Chun-Lan Chen ◽  
Yan Huang ◽  
Miguel Angel Martinez-Garcia ◽  
Jing-Jing Yuan ◽  
Hui-Min Li ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Quantitative Polymerase Chain Reaction ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Viral Loads ◽  
Barr Virus ◽  
Opportunistic Bacteria ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Background Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. Methods We collected induced sputum in healthy controls and spontaneous sputum at 3–6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. Results We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1β (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor–α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. Conclusions Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression.

scholarly journals Plasma Macrophage Inhibitory Cytokine-1 as a Complement of Epstein-Barr Virus Related Markers in Identifying Nasopharyngeal Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382095699
Author(s):  
Shan Xing ◽  
Huilan Li ◽  
Yingqi Pi ◽  
Tao Zeng ◽  
Qi Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Copy Number ◽  
Epstein Barr Virus ◽  
Normal Subjects ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Barr Virus ◽  
Healthy Donors ◽  
Ebv Dna ◽  
Epstein Barr

Background: We evaluated the diagnostic value of plasma Macrophage inhibitory cytokine-1 (MIC-1) in distinguishing patients with nasopharyngeal carcinoma (NPC) and explored its complementary role with widely used Epstein-Barr virus (EBV) related markers, EBV capsid antigen-specific IgA (VCA-IgA) and EBV copy number. Methods: ELISA was used to analyze the plasma MIC-1 levels in 190 NPC patients, 72 VCA-IgA-positive healthy donors (VP), and 219 normal subjects with negative VCA-IgA (VN). 10 pairs of plasma samples before and after radiotherapy were also included. Results: The plasma MIC-1 levels were significantly higher in NPC patients (Median: 678.39 ng/mL) than those in VN and VP (310.29 and 294.59, p < 0.001). Receiver operating characteristic (ROC) curves of the MIC-1 concentrations revealed that the area under the ROC curve (AUC) was 0.790 (95% confidence interval [CI]: 0.748-0.832), with a sensitivity of 63.7%, and a specificity of 85.9% respectively, for distinguishing NPC patients from the healthy donors. Similarly, between NPC and VP, ROC was 0.796 (0.738-0.853) with sensitivity of 63.7%, and specificity of 88.9%. In addition, between NPC and VN, ROC was 0.788(0.744-0.832) with sensitivity of 63.7%, and specificity of 84.9%. Further, we found that MIC-1 could complement VCA-IgA and EBV DNA markers, with a negative rate of 88.9% in VCA-IgA-positive healthy controls, and a positive rate of 59.0% in EBV DNA negative NPC patients, respectively. Also, the MIC-1 plasma concentration dropped significantly after radiotherapy ( p = 0.027). Conclusions: MIC-1 can complement VCA-IgA titers and EBV DNA copy number tests in NPC detection, improve identification of EBV DNA-negative NPC patients, and distinguish NPC from VCA -IgA positive healthy controls.

Phase II Study of Neoadjuvant Carboplatin and Paclitaxel Followed by Radiotherapy and Concurrent Cisplatin in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: Therapeutic Monitoring With Plasma Epstein-Barr Virus DNA

2004 ◽  
Vol 22 (15) ◽  
pp. 3053-3060 ◽  
Author(s):  
Anthony T.C. Chan ◽  
Brigette B.Y. Ma ◽  
Y.M. Dennis Lo ◽  
S.F. Leung ◽  
W.H. Kwan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Treatment Response ◽  
Epstein Barr Virus ◽  
Quantitative Polymerase Chain Reaction ◽  
Therapeutic Monitoring ◽  
Tumor Control ◽  
Weekly Cycle ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Purpose To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. Patients and Methods Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. Conclusion This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

Characterization of Epstein-Barr virus–infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4055-4063 ◽  
Author(s):  
Jie Yang ◽  
Qian Tao ◽  
Ian W. Flinn ◽  
Paul G. Murray ◽  
Linda E. Post ◽  
...  
Keyword(s):  
Viral Load ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Viral Gene Expression ◽  
Lymphoproliferative Disease ◽  
Viral Gene ◽  
Healthy Controls ◽  
Viral Loads ◽  
Barr Virus ◽  
Epstein Barr

Post-transplantation lymphoproliferative disease (PTLD) is associated with Epstein-Barr virus (EBV). Quantitative and qualitative differences in EBV in peripheral blood mononuclear cells (PBMCs) of PTLD patients and healthy controls were characterized. A quantitative competitive polymerase chain reaction (QC-PCR) technique confirmed previous reports that EBV load in PBMCs is increased in patients with PTLD in comparison with healthy seropositive controls (18 539 vs 335 per 106 PBMCs, P = .0002). The average frequency of EBV-infected cells was also increased (271 vs 9 per 106 PBMCs, P = .008). The distribution in numbers of viral genome copies per cell was assessed by means of QC-PCR at dilutions of PBMCs. There was no difference between PTLD patients and healthy controls. Similarly, no differences in the patterns of viral gene expression were detected between patients and controls. Finally, the impact of therapy on viral load was analyzed. Patients with a past history of PTLD who were disease-free (after chemotherapy or withdrawal of immunosuppression) at the time of testing showed viral loads that overlapped with those of healthy seropositive controls. Patients treated with rituximab showed an almost immediate and dramatic decline in viral loads. This decline occurred even in patients whose PTLD progressed during therapy. These results suggest that the increased EBV load in PBMCs of PTLD patients can be accounted for by an increase in the number of infected B cells in the blood. However, in terms of viral copy number per cell and pattern of viral gene expression, these B cells are similar to those found in healthy controls. Disappearance of viral load with rituximab therapy confirms the localization of viral genomes in PBMCs to B cells. However, the lack of relationship between the change in viral load and clinical response highlights the difference between EBV-infected PBMCs and neoplastic cells in PTLD.

Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence

Blood ◽  
2009 ◽  
Vol 113 (25) ◽  
pp. 6372-6381 ◽  
Author(s):  
Sridhar Chaganti ◽  
Emily M. Heath ◽  
Wolfgang Bergler ◽  
Michael Kuo ◽  
Maike Buettner ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Primary Infection ◽  
Epstein Barr Virus ◽  
Quantitative Polymerase Chain Reaction ◽  
Viral Loads ◽  
Barr Virus ◽  
Memory Pool ◽  
Epstein Barr ◽  
B Cell Subsets

AbstractEpstein-Barr virus (EBV) persists in the immune host by preferentially colonizing the isotype-switched (IgD−CD27+) memory B-cell pool. In one scenario, this is achieved through virus infection of naive (IgD+CD27−) B cells and their differentiation into memory via germinal center (GC) transit; in another, EBV avoids GC transit and infects memory B cells directly. We report 2 findings consistent with this latter view. First, we examined circulating non–isotype-switched (IgD+CD27+) memory cells, a population that much evidence suggests is GC-independent in origin. Whereas isotype-switched memory had the highest viral loads by quantitative polymerase chain reaction, EBV was detectable in the nonswitched memory pool both in infectious mononucleosis (IM) patients undergoing primary infection and in most long-term virus carriers. Second, we examined colonization by EBV of B-cell subsets sorted from a unique collection of IM tonsillar cell suspensions. Here viral loads were concentrated in B cells with the CD38 marker of GC origin but lacking other GC markers CD10 and CD77. These findings, supported by histologic evidence, suggest that EBV infection in IM tonsils involves extrafollicular B cells expressing CD38 as an activation antigen and not as a marker of ectopic GC activity.

The rational specimen for the quantitative detection of Epstein-Barr virus DNA load

2019 ◽  
Vol 57 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Wang Kedi ◽  
Xu Dongjiang ◽  
Lv Zhi ◽  
Gao Yan ◽  
Jia Kun ◽  
...  
Keyword(s):  
Viral Load ◽  
Epstein Barr Virus ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Diagnostic Value ◽  
Quantitative Detection ◽  
Peripheral Blood Mononuclear ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Background Epstein-Barr virus (EBV) DNA load monitoring in blood is essential for the diagnosis of EBV-associated diseases. However, the best-suited blood compartment for detection is still under discussion. The aim of this study was to evaluate the diagnostic value of EBV-DNA load in peripheral blood mononuclear cells (PBMC), plasma and whole blood (WB) samples. Methods A total of 156 patients, including 45 patients with infectious mononucleosis (IM), 57 patients with EBV-associated hemophagocytic lymphohistiocytosis (HLH) and 54 patients with post-transplant lymphoproliferative disorders (PTLD), were enrolled in this study. The EBV-DNA load in PBMC, plasma and WB samples were measured with real-time quantitative polymerase chain reaction (PCR). Results EBV-DNA load of patients with HLH showed no statistical difference in PBMC, plasma and WB samples, while patients with IM and PTLD showed a higher viral load in PBMC samples. The strongest correlation of EBV-DNA level was found between PBMC and WB samples among patients with IM, HLH and PTLD. The follow-up of EBV-DNA showed that the viral load became negative along with the recovery from the disease, while that in WB and PBMC would remain positive for a long time. Conclusions For the diagnosis and monitoring of EBV-DNA, the type of specimen should be chosen reasonably according to the disease. As for IM and HLH, plasma is recommended to quantify the EBV-DNA load, while PBMC and plasma are preferred in PTLD.

scholarly journals Impact of Plasma Epstein-Barr Virus-DNA and Tumor Volume on Prognosis of Locally Advanced Nasopharyngeal Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Meng Chen ◽  
Li Yin ◽  
Jing Wu ◽  
Jia-Jia Gu ◽  
Xue-Song Jiang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Tumor Volume ◽  
Quantitative Polymerase Chain Reaction ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV-) DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR) amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx), the lymph node lesions (GTVnd), and the total GTV before treatment were 72.46, 23.26, and 106.25 cm3, respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P<0.01). The 2-year overall survival (OS) rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P=1.000), and the disease-free survival (DFS) rates were 94.4% and 80.8% (P=0.044), respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

Characterization of Epstein-Barr virus–infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4055-4063 ◽  
Author(s):  
Jie Yang ◽  
Qian Tao ◽  
Ian W. Flinn ◽  
Paul G. Murray ◽  
Linda E. Post ◽  
...  
Keyword(s):  
Viral Load ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Viral Gene Expression ◽  
Lymphoproliferative Disease ◽  
Viral Gene ◽  
Healthy Controls ◽  
Viral Loads ◽  
Barr Virus ◽  
Epstein Barr

Abstract Post-transplantation lymphoproliferative disease (PTLD) is associated with Epstein-Barr virus (EBV). Quantitative and qualitative differences in EBV in peripheral blood mononuclear cells (PBMCs) of PTLD patients and healthy controls were characterized. A quantitative competitive polymerase chain reaction (QC-PCR) technique confirmed previous reports that EBV load in PBMCs is increased in patients with PTLD in comparison with healthy seropositive controls (18 539 vs 335 per 106 PBMCs, P = .0002). The average frequency of EBV-infected cells was also increased (271 vs 9 per 106 PBMCs, P = .008). The distribution in numbers of viral genome copies per cell was assessed by means of QC-PCR at dilutions of PBMCs. There was no difference between PTLD patients and healthy controls. Similarly, no differences in the patterns of viral gene expression were detected between patients and controls. Finally, the impact of therapy on viral load was analyzed. Patients with a past history of PTLD who were disease-free (after chemotherapy or withdrawal of immunosuppression) at the time of testing showed viral loads that overlapped with those of healthy seropositive controls. Patients treated with rituximab showed an almost immediate and dramatic decline in viral loads. This decline occurred even in patients whose PTLD progressed during therapy. These results suggest that the increased EBV load in PBMCs of PTLD patients can be accounted for by an increase in the number of infected B cells in the blood. However, in terms of viral copy number per cell and pattern of viral gene expression, these B cells are similar to those found in healthy controls. Disappearance of viral load with rituximab therapy confirms the localization of viral genomes in PBMCs to B cells. However, the lack of relationship between the change in viral load and clinical response highlights the difference between EBV-infected PBMCs and neoplastic cells in PTLD.

Epstein–Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity

Lupus ◽  
2020 ◽  
Vol 29 (10) ◽  
pp. 1263-1269
Author(s):  
Deniz Aygun ◽  
Mert Ahmet Kuskucu ◽  
Sezgin Sahin ◽  
Amra Adrovic ◽  
Kenan Barut ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Systemic Lupus ◽  
Barr Virus ◽  
Bk Polyomavirus ◽  
Ebv Dna ◽  
Epstein Barr

Objectives Clinical and laboratory investigations have revealed that Epstein–Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease – juvenile systemic sclerosis (jSS) – and healthy individuals. Methods Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. Results A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. Conclusion The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.

scholarly journals Validation of a Highly Sensitive qPCR Assay for the Detection of Plasma Cell-Free Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma Diagnosis

2020 ◽  
Vol 27 (3) ◽  
pp. 107327482094428
Author(s):  
Vu Nguyen Quynh Anh ◽  
Nguyen Van Ba ◽  
Do Tram Anh ◽  
Nguyen Dinh Ung ◽  
Nguyen Hoang Hiep ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Plasma Cell ◽  
Epstein Barr Virus ◽  
Clinical Performance ◽  
Quantitative Polymerase Chain Reaction ◽  
Qpcr Assay ◽  
Barr Virus ◽  
Highly Sensitive ◽  
Ebv Dna ◽  
Epstein Barr

Quantification of plasma cell-free Epstein Barr virus DNA (cf EBV DNA) has been suggested as a promising liquid biopsy assay for screening and early detection of nasopharyngeal carcinoma (NPC). However, the diagnostic value of this assay is currently not known in the population of Vietnam, one of the countries which contributed the most to the NPC cases. Herein, we have reported a highly sensitive quantitative polymerase chain reaction (qPCR)-based assay targeting cf EBV DNA for the detection of NPC. A standard curve with linear regression, R 2 = 0.9961 (range: 25-150 000 copies/mL) and a detection limit of 25 copies/mL were obtained using an EBV standard panel provided by the Chinese University of Hong Kong. The clinical performance of this assay was assessed using plasma samples obtained from 261 Vietnamese individuals. The optimized qPCR assay detected cf EBV DNA in plasma with a sensitivity of 97.4% and a specificity of 98.2%. The absolute quantitative results of pretreatment cf EBV DNA and patient overall clinical stages were statistically correlated ( P < .05). In summary, the remarkably high sensitivity and specificity of our optimized qPCR assay strongly supports the wide use of cf EBV DNA quantification as a routine noninvasive method in early diagnosis and management of patients with NPC.

Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies

2000 ◽  
Vol 111 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Kenny I. K. Lei ◽  
Lisa Y.S. Chan ◽  
Wing Y. Chan ◽  
Philip J. Johnson ◽  
Y. M. Dennis Lo
Keyword(s):  
Quantitative Analysis ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Lymphoid Malignancies ◽  
Ebv Dna ◽  
Epstein Barr
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