EBV DNA increase in COVID-19 patients with impaired Lymphocyte subpopulation count

The aim of the study was to assess the prevalence of DNA viruses (HSV I and II, CMV, EBV, HPV6.11, HPV16 and HPV18) in the native oral mucosa of healthy volunteers (n=50; 30 men (60.0%), 20 women (40.0%); 25—74 years, median age — 55.0 years (95% CI 47.60-56.76)). All samples of the normal oral mucosa were detected by real-time PCR to detect viral DNA. The majority of the examined — 76% (33/50) — revealed the DNA: one type of viral DNA in 17 (38.00%) of the examined, a combination of the two types in 14 (28.00%). In the normal oral mucosa, DNA of Epstein-Barr virus was significantly more often detected: 15 (30.00%) (p = 0.0276) and human papilloma viruses 27 (54.00%) (p <0.0001), especially HPV-18 (24 (48.00%)): mono-association in 9 (18.00%) examined and in 7 (14.00%) in combination with EBV DNA (p = 0.0253).

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Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

Infectious Agents and Cancer ◽

10.1186/s13027-021-00353-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Amina Gihbid ◽

Raja Benzeid ◽

Abdellah Faouzi ◽

Jalal Nourlil ◽

Nezha Tawfiq ◽

...

Keyword(s):

Prognostic Factors ◽

Lymph Node ◽

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Disease Stage ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr ◽

Pre Treatment ◽

Moroccan Patients

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

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Age-stratified pediatric reference values of lymphocytes in the Moroccan population

Human Antibodies ◽

10.3233/hab-200432 ◽

2020 ◽

pp. 1-10

Author(s):

Aicha El Allam ◽

Sara El Fakihi ◽

Hicham Tahoune ◽

Karima Sahmoudi ◽

Houria Bousserhane ◽

...

Keyword(s):

T Lymphocytes ◽

Reference Values ◽

Blood Lymphocyte ◽

Healthy Subjects ◽

Lymphocyte Subsets ◽

Age Groups ◽

Lymphocyte Subpopulation ◽

Study Group ◽

Moroccan Population ◽

Helper T Lymphocytes

The number of circulating lymphocytes is altered in a number of diseases including either increase (lymphocytosis) or decrease (lymphocytopenia). Therefore, the assessment of total blood lymphocyte numbers and the relative distribution of lymphocyte subsets is a critical front-line tool in the clinical diagnosis of a number of diseases, including pediatric diseases and disorders. However, the interpretation of this data requires comparison of patient’s results to reliable reference values. Blood lymphocyte subpopulation numbers are also subject to genetic polymorphisms, immunogenic and environmental factors and vary greatly between populations. While the best practice reference values should be established within local representative populations of healthy subjects, to date, Caucasian reference values are used in Morocco due to the absence of indigenous reference values. Potential differences in blood lymphocyte subpopulation reference values between Caucasian versus Moroccan populations can adversely affect the diagnosis of pediatric and childhood diseases and disorders such as primary immunodeficiency (PID) in Morocco. OBJECTIVE: The aim of this study was to establish the age-stratified normal reference values of blood lymphocyte subsets for the pediatric Moroccan population. METHODS: We measured the concentration of lymphocyte subpopulations by flow cytometry from 83 Moroccan healthy subjects stratified into 5 age groups of 0–1, 1–2, 2–6, 6–12 and > 12–18 (adult). RESULTS: The absolute and relative amounts of the main lymphocyte subsets of T-cells, B cells and Natural Killer (NK) cells were measured and compared to previously described reference values from Cameroonian, Turkish, American and Dutch populations. Additionally, we also observed an age-related decline in the absolute population sizes of lymphocyte subsets within our study group. Relative proportions of CD3+CD4+ helper T lymphocytes decreased with increasing age and by 12 years-adult age, both proportions of CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, as well as CD3-CD19+ B lymphocytes were also decreased. Finally, we compared the median values and range of our Moroccan study group with that of published results from Cameroon, Turkey, USA and Netherlands and observed significant differences in median and mean values of absolute number and relative proportions of lymphocyte subsets especially at 0–1 years and 1–2 years age groups. Above age 12 years, the Moroccan values were lower. For NK cells, the Moroccan values are also lower. CONCLUSIONS: The results of this study have a significant impact in improving the threshold values of the references intervals routinely used in the diagnosis of paediatric diseases such as PIDs or mother-to-child transmitted HIV within the Moroccan population.

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Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

Microbiology Research ◽

10.3390/microbiolres12010011 ◽

2021 ◽

Vol 12 (1) ◽

pp. 150-156

Author(s):

Soehartati A. Gondhowiardjo ◽

Handoko ◽

Marlinda Adham ◽

Lisnawati Rachmadi ◽

Henry Kodrat ◽

...

Keyword(s):

Viral Load ◽

Tumor Cells ◽

Epstein Barr Virus ◽

Tumor Volume ◽

Nasopharyngeal Cancer ◽

Dna Quantification ◽

Barr Virus ◽

Nasopharyngeal Biopsy ◽

Ebv Dna ◽

Epstein Barr

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

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The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis

Cancer Cell International ◽

10.1186/s12935-021-01862-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Weixing Liu ◽

Gui Chen ◽

Xin Gong ◽

Yingqi Wang ◽

Yaoming Zheng ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Test Performance ◽

Meta Analysis ◽

Diagnostic Value ◽

Cochrane Library ◽

Control Group ◽

Summary Receiver Operating Characteristic ◽

Ebv Dna ◽

The Difference ◽

Sensitivity Specificity

Abstract Background Numerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC. Methods PROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek’s funnel plot asymmetry test. Results Forty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+ LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73–0.77), 0.96 (95% CI 0.95–0.97), 14.66 (95% CI 9.97–21.55), 0.19 (95% CI 0.13–0.28), 84 (95% CI 50.45–139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54–0.57), 0.96 (95% CI 0.96–0.97), 12.91 (95% CI 9.55–17.45), 0.35 (95% CI 0.29–0.43), 39.57 (95% CI 26.44–59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84–0.85), 0.89 (95% CI 0.88–0.89), 6.73 (95% CI5.38–8.43), 0.17 (95% CI 0.12–0.23), 43.03 (95% CI 31.51–58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85–0.88), 0.87 (95% CI 0.88–0.90), 7.55 (95% CI 5.79–9.87), 0.16 (95% CI 0.13–0.19), 50.95 (95% CI 34.35–75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69–0.71), 0.94 (95% CI 0.94–0.95), 9.84 (95% CI 8.40–11.54), 0.25 (95% CI 0.21–0.31), 40.59 (95% CI 32.09–51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P < 0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P > 0.05). Conclusions EBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.

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Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

BMC Cancer ◽

10.1186/s12885-021-08408-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen-Jie Chen ◽

Wen-Na Xu ◽

Hai-Yun Wang ◽

Xiao-Xia Chen ◽

Xue-Qi Li ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Screening Program ◽

Southern China ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

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Long-Term Prognostic Effects of Plasma EBV DNA Load after Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.07.908 ◽

2018 ◽

Vol 102 (3) ◽

pp. e284

Author(s):

Y.C. Liu ◽

W.Y. Wang ◽

J.C. Lin

Keyword(s):

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Ebv Dna

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Reepithelialization of Orthotopic Tracheal Allografts Prevents Rejection after Withdrawal of Immunosuppression

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940511400406 ◽

2005 ◽

Vol 114 (4) ◽

pp. 279-288 ◽

Cited By ~ 18

Author(s):

Satish Govindaraj ◽

Elena Fedorova ◽

Eric M. Genden ◽

Houtan Chaboki ◽

Jonathan S. Bromberg ◽

...

Keyword(s):

Electron Microscopy ◽

Cyclosporine A ◽

Allograft Rejection ◽

Lymphocyte Subpopulation ◽

Ciliated Epithelium ◽

Prior Work ◽

Cellular Infiltrate ◽

Tracheal Transplantation

Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.

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