Does the Epstein–Barr Virus Play a Role in the Pathogenesis of Graves’ Disease?

Graves’ disease (GD) it the most common chronic organ-specific thyroid disorder without a fully recognized etiology. The pathogenesis of the disease accounts for an interaction between genetic, environmental, and immunological factors. The most important environmental factors include viral and bacterial infections. The Epstein-Barr virus (EBV) is one of the most common latent human viruses. Literature has suggested its role in the development of certain allergic and autoimmune diseases. EBV also exhibits oncogenic properties. The aim of the study was to analyze and compare the presence of EBV DNA in peripheral blood mononuclear cells (PBMCs) in patients with newly recognized GD and to find a correlation between EBV infection and the clinical picture of GD. The study included 39 untreated patients with newly diagnosed GD and a control group of 20 healthy volunteers who were gender and age matched. EBV DNA was detected with reverse transcription polymerase chain reaction (RT PCR) assay. The studies showed a significantly higher incidence of EBV copies in PBMCs among GD patients compared to the control group. Whereas, no significant correlations were found between the incidence of EBV copies and the evaluated clinical parameters. Our results suggest a probable role of EBV in GD development. EBV infection does not affect the clinical picture of Graves’ disease.

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THE VALUE OF THE IMMUNE RESPONSE IN PATIENTS WITH EBV INFECTIOUS MONONUCLEOSIS IN PREDICTING THE COURSE AND EFFICACY OF ANTIVIRAL AND IMMUNO IMMUNOCORRECTING THERAPY

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40689 ◽

2013 ◽

Vol 18 (1) ◽

pp. 7-14

Author(s):

T. A. Svintsova ◽

D. M. Sobchak ◽

O. V. Korochkina ◽

G. A Kravchenko ◽

V. V Novikov

Keyword(s):

Immune Response ◽

Infectious Mononucleosis ◽

Epstein Barr Virus ◽

Mononuclear Cells ◽

Polyclonal Antibodies ◽

Severity Of Illness ◽

Control Group ◽

Differentiation Antigens ◽

Barr Virus ◽

Epstein Barr

The indices of immune response were studied in 68 patients with infectious mononucleosis caused by the Epstein-Barr virus (35 males, 33 females) aged 18 to 30 years. Materials and methods. The content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50, sHLAI, sCD54) has been studied with enzyme immunoassay using monoclonal antibodies Mab IC0-20 and polyclonal antibodies to the antigens of the mononuclear cells of the peripheral blood. The control group included 60 healthy volunteers matched for age and sex with the main group. The aim of this study is the assessment of the content of soluble forms of differentiation antigens in patients with infectious mononucleosis caused by Epstein-Barr virus, depending on gender, age, severity of illness, comorbidities, laboratory values, the presence of viral DNA, as well as a demonstration of their value in predicting the course and outcome of the disease and the efficacy of antiviral and immunocorrecting therapy. In patients with negative results of DNA indication of EBV a significant increase in the content of soluble forms of differentiation antigens characterizing the adhesion of leukocytes (sCD18), the activity of T-lymphocytes (sCD50), the recognition of foreign antigens (sHLAI) in the blood in comparison with patients with a positive DNA indication of EBV was determined. Conclusion. According to the results of this performed work the criterion for an adequate immune response in patients with infectious mononucleosis caused by the Epstein-Barr virus was found to be the increase of the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54). In patients with exanthema, tonsillar syndrome, leukocytosis, elevation of transaminases and the presence of antibodies to capsid antigen (a/VCAIgM) the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54), was higher than in patients without such symptoms. In the treatment with cycloferon in patients with cyclic course of EBV infectious mononucleosis the content of sHLAI and sCD54 at 2nd-4th weeks of treatment increased by 1.5-2 times compared with the corresponding values before treatment. In patients with reactivation of the disease monotonically low indices of all studied soluble forms of differentiation antigens persisted over the 4 weeks during patients following up. In patients with infectious mononucleosis caused by Epstein-Barr virus, the dynamics of sHLAI and sCD54 after 2-4 weeks of treatment serves as secondary efficacy endpoint of antiviral, immunomodulatory therapy and the formation of the cyclic course of the disease.

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Clinical Warning of Hemophagocytic Syndrome Caused by Epstein-barr Virus

10.21203/rs.3.rs-47979/v1 ◽

2020 ◽

Author(s):

Jinjin Shi ◽

Chu Chu ◽

Min Yu ◽

Dandan Zhang ◽

Yuqin Li ◽

...

Keyword(s):

Laboratory Tests ◽

Epstein Barr Virus ◽

Hemophagocytic Syndrome ◽

Clinical Manifestations ◽

Prognostic Indicator ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr ◽

D Dimer

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

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Transient Immunodeficiency During Asymptomatic Epstein-Barr Virus Infection

PEDIATRICS ◽

10.1542/peds.71.6.964 ◽

1983 ◽

Vol 71 (6) ◽

pp. 964-967

Author(s):

THOMAS J. BOWEN ◽

RALPH J. WEDGWOOD ◽

HANS D. OCHS ◽

WERNER HENLE

Keyword(s):

Epstein Barr Virus ◽

Mononuclear Cells ◽

Epstein Barr Virus Infection ◽

Peripheral Blood Mononuclear ◽

Immunoglobulin Synthesis ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr

In vivo and in vitro humoral and cellular immune responses were studied in a 2½-year-old girl immediately before, during, and after an asymptomatic infection with Epstein-Barr virus. During the acute EBV infection, the patient's peripheral blood mononuclear cells were deficient in immunoglobulin synthesis and suppressed the in vitro immunoglobulin synthesis of normal allogeneic cells. In vitro mitogen transformation of lymphocytes was reduced. In vivo antibody responses to the T cell-dependent antigens bacteriophage φX 174 and Keyhole limpet hemocyanin were markedly depressed. These studies suggest that suppressor cells induced during acute EBV infection not only suppress immunoglobulin synthesis in vitro, but also interfere with in vivo antibody synthesis.

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Epstein–Barr virus and regulatory T cells in Egyptian paediatric patients with acute B lymphoblastic leukaemia

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-203803 ◽

2016 ◽

Vol 70 (2) ◽

pp. 120-125 ◽

Cited By ~ 3

Author(s):

Mohamed E Ateyah ◽

Mona E Hashem ◽

Mohamed Abdelsalam

Keyword(s):

Lymphoblastic Leukaemia ◽

Epstein Barr Virus ◽

Acute Infection ◽

Treg Cells ◽

Control Group ◽

Healthy Children ◽

Barr Virus ◽

Ebv Infection ◽

High Incidence ◽

Epstein Barr

ObjectiveAcute B lymphoblastic leukaemia (B-ALL) is the most common type of childhood malignancy worldwide but little is known of its origin. Recently, many studies showed both a high incidence of Epstein–Barr virus (EBV) infection and high levels of CD4+CD25+Foxp3+(Treg cells) in children with B-ALL. In our study, we investigated the possible relationship between EBV infection and the onset of B-ALL, and its relation to expression of CD4+, CD25high+Foxp3+ T regulatory cells.Subject and methodsWe analysed expression and mean fluorescence intensity (MFI) of Treg cells in peripheral blood of 45 children with B-ALL and in 40 apparently healthy children as a control, using flow cytometry. Serum anti-EBV viral capsid antigen (VCA) IgG, anti-EBV nuclear antigen (EBNA) IgG (for latent infection) and anti-EBV VCA IgM (for acute infection) were investigated using ELISA.ResultsAnalysis of the Treg cells population in patients and controls revealed that expression of CD4+ CD25high+ T lymphocytes was higher in patients than in controls (mean±SD 15.7±4.1 and 10.61±2.6 in patients and controls, respectively, and MFI of Foxp3 was 30.1±7.1 and 16.7±3.7 in patients and controls, respectively (p<0.001)). There was a high incidence of latent EBV infection in patients (31%) compared with controls (10%) while the incidence of acute infection was 12% in patients and 0% in the control group. To study the role of latent EBV infection in the pathogenesis of acute B-ALL, OR was calculated (OR=4.06, coefficient index 1.2–13.6).ConclusionsThese findings suggest a possible role for Treg cells and EBV in the pathogenesis of B-ALL. Further studies are needed on the possible mechanisms of tumour genesis related to Treg cells and EBV in children with B-ALL.

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HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

10.21203/rs.2.22776/v3 ◽

2020 ◽

Author(s):

Yue Song ◽

Jingshi Wang ◽

Yini Wang ◽

Zhao Wang

Keyword(s):

Survival Rate ◽

Hemophagocytic Lymphohistiocytosis ◽

Median Survival Time ◽

Epstein Barr Virus ◽

Control Group ◽

Short Term ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr ◽

Better Than

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH. Methods: A retrospective case-control study of refractory EBV-HLH patients with GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 2018.Results: There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs group, EBV-DNA decreased significantly after 2 weeks (p=0.001) and 4 weeks (p=0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w=0.011, p4w=0.145). The median survival time in the infusion group was 20.4 weeks [95%CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95%CI 0-24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p=0.008; 3-month 83.33% vs. 47.09%, p=0.012), but there was no difference in OS (p=0.287). Conclusions: Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.

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HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

10.21203/rs.2.22776/v2 ◽

2020 ◽

Author(s):

Yue Song ◽

Jingshi Wang ◽

Yini Wang ◽

Zhao Wang

Keyword(s):

Survival Rate ◽

Hemophagocytic Lymphohistiocytosis ◽

Median Survival Time ◽

Epstein Barr Virus ◽

Control Group ◽

Short Term ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr ◽

Better Than

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH. Methods: A retrospective case-control study of refractory EBV-HLH patients with GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 2018. Results: There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs group, EBV-DNA decreased significantly after 2 weeks (p=0.001) and 4 weeks (p=0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w=0.011, p4w=0.145). The median survival time in the infusion group was 20.4 weeks [95%CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95%CI 0-24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p=0.008; 3-month 83.33% vs. 47.09%, p=0.012), but there was no difference in OS (p=0.287). Conclusions: Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.

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Link of Nasopharyngeal Carcinoma and Epstein-Barr Virus

Biology Medicine & Natural Product Chemistry ◽

10.14421/biomedich.2018.72.51-55 ◽

2018 ◽

Vol 7 (2) ◽

pp. 51-55

Author(s):

Sugiyanto Sugiyanto ◽

Lina Aryati ◽

Fajar Adi Kusumo ◽

Mardiah Suci Hardianti

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Carcinoma Cells ◽

Lymphoid Cells ◽

Epithelial Tissue ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr ◽

Basic Level

Nasopharyngeal Carcinoma (NPC) is a cancer that occurs in nasopharynx which is associated with Epstein-Barr Virus (EBV). Mutation agents in nasopharyngeal neoplasms occur because of EBV infection. Transformation of B-cells due to EBV causes hormone imbalance in lymphoid cells or nasopharyngeal epithelial tissue. Rates of EBV infection have been shown to be prognostic to NPC. The basic level of EBV DNA can be used for stratification prognosis, with higher titers showing greater disease severity and worse outcomes. With mathematical models, there is a correlation between the increase in Epstein-Barr Virus and the increase in Invasive Carcinoma Cells or increase in Nasopharyngeal Carcinoma Cells.

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Increasing Epstein-Barr virus infection in Chinese children: A single institutional based retrospective study.

F1000Research ◽

10.12688/f1000research.15544.1 ◽

2018 ◽

Vol 7 ◽

pp. 1211 ◽

Cited By ~ 1

Author(s):

Kiran Devkota ◽

Maio He ◽

Meng Yi Liu ◽

Yan Li ◽

You Wei Zhang

Keyword(s):

Retrospective Study ◽

High Risk ◽

Virus Infection ◽

Epstein Barr Virus ◽

Severe Illness ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr

The Epstein-Barr virus (EBV) is a common virus in humans and the most common causative agent of Infectious Mononucleosis. EBV primary infection has recently risen in some countries and children below 2 years of age are highly susceptible. The clinical manifestations in children with EB virus infection involve multiple systems, causing severe illness, meaning attention should be paid during diagnosis and treatment. Objective: This single institution based retrospective study was carried out with the aim of estimating the overall prevalence of EBV infection and identifying high-risk age group among children. Methods: This study include total 253 patients under 15 years of age found to be positive for EBV DNA by PCR who were admitted to the Pediatrics Department of Renmin Hospital,(Shiyan, China) during a 4-year period from 2014 to 2017. Patients were divided into three groups; 0-<4years, 4-<6years and 6-<15years. We then calculated the percentage and prevalence of EBV DNA-positive cases. Results: The yearly EBV prevalence rate was 4.99 per 1000 admissions in 2014, 6.97 per 1000 admissions in 2015, 10.42 per 1000 admissions in 2016, and 12.16 per 1000 admissions in 2017. Out of 253 EBV-positive cases, those under 4 years had the highest rate of EBV infection (74.7%). The rate drops to 11.06% in the 4-6 years group, and was 14.22% in the 6-15 years group. Those between 6 months and 1 year are those at the highest risk. Conclusion: The rate of hospital admission of children due to EBV infection is increasing day by day. Children under 4 years of age are highly susceptible to infection and children of age between 6 months and 1 year are the high-risk group for EBV infection.

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Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus

10.21203/rs.3.rs-47979/v3 ◽

2020 ◽

Author(s):

Jinjin Shi ◽

Chu Chu ◽

Min Yu ◽

Dandan Zhang ◽

Yuqin Li ◽

...

Keyword(s):

Laboratory Tests ◽

Epstein Barr Virus ◽

Hemophagocytic Syndrome ◽

Clinical Manifestations ◽

Prognostic Indicator ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr ◽

D Dimer

Abstract Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3 + , CD4 + , CD8 + , NK, and CD3-CD19 + cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

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Demonstration of Epstein-Barr Virus DNA in Acetowhite Lesions of the Vulva

International Journal of STD & AIDS ◽

10.1177/095646249400500107 ◽

1994 ◽

Vol 5 (1) ◽

pp. 25-28 ◽

Cited By ~ 7

Author(s):

E Voog ◽

A Ricksten ◽

G B Löwhagen ◽

A Ternesten

Keyword(s):

Human Papilloma Virus ◽

Epstein Barr Virus ◽

Control Group ◽

Papilloma Virus ◽

Hpv Dna ◽

Barr Virus ◽

Oral Hairy Leukoplakia ◽

Hairy Leukoplakia ◽

Ebv Dna ◽

Epstein Barr

Acetowhite lesions in the vulva disclosing koilocytosis have been related to infection by human papilloma virus (HPV). Because of the clinical resemblance of these lesions to oral hairy leukoplakia (OHL), and EBV-manifestation, 23 women with acetowhite koilocytotic lesions in the vulva were examined. The PCR-technique was used to detect EBV DNA as well as HPV DNA in 17% of 23 patients examined. In a control group of 19 patients EBV DNA was detected in 11% and HPV DNA in 42% of cell samples from normal vulvar mucosa. EBV DNA has not previously been demonstrated in the vulvar mucosa, and this virus might be related to subclinical acetowhite lesions.

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