Epstein-Barr Virus Capsid Antigen Research Articles

Evaluation of Epstein-Barr Virus Indirect Immunofluorescence Assay Results

Aim: Epstein-Barr Virus (EBV) causes Infectious Mononucleosis (IM) and chronic active EBV infections, malignant diseases such as Burkitt’s lymphoma, nasopharyngeal carcinoma, and posttransplant lymphoproliferative disease. More than 90% of children are infected with EBV until the age of six. The aim of this study was to diagnose EBV infection using Indirect Immunofluorescence Assay (IIFA) method and to evaluate these patients clinically. Methods: The tests were studied by using EBV Indirect Immunofluorescence Assay (IIFA) method. A total of 247 patients, 186 adults, and 61 children, were included in the study. Results: Five (2.7%) of the adults were EBV-Capsid Antigen (EBV-CA) IgM positive, 175 (94.1%) were IgG positive and 6 (3.2%) were seronegative. 10 (16.4%) of the child patients were IgM positive, which is considered as an acute IM infection marker, whereas the child patients had a significantly higher IgM rate than adults (p <0.001). 39 (63.9%) of the child patients were IgG positive and 12 (19.7%) of them were seronegative. The rate of IgG positivity in children was significantly lower than in adults (p <0.001). There was no significant difference between the genders in terms of IgM and IgG positivity rates in both adults and children (p >0.05 for each). Conclusion: These results suggest that the presence of an acute EBV infection should be considered when the patient has viral diseases with similar clinical picture especially for children.

Clinical Validity of Serum Antibodies to SARS-CoV-2 : A Case-Control Study.

The clinical utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remains undefined. To determine the clinical validity and utility of SARS-CoV-2 antibodies. Case-control study. First month of testing for coronavirus disease 2019 (COVID-19) by using a nucleic acid amplification test (NAAT) on nasopharyngeal swabs at the Johns Hopkins Hospital, Baltimore, Maryland (11066 persons). Of the 11066 tested persons, 115 (1%) were hospitalized adults investigated for COVID-19. Clinical record review was performed to classify them into a COVID-19 case group (n= 60) or a non-COVID-19 control group (n= 55). The laboratory control groups comprised 513 persons not tested by NAAT: 160 healthy laboratory employees, 101 persons positive for IgG antibodies against Epstein-Barr virus capsid antigen, 215 positive for thyroperoxidase antibody, and 37 positive for rheumatoid factor. Serum IgG and IgA antibodies against SARS-CoV-2 spike protein were detected by using enzyme-linked immunosorbent assay. Sensitivity and specificity of the SARS-CoV-2 IgG assay were 0.976 (95% CI, 0.928 to 0.995) and 0.988 (CI, 0.974 to 0.995), respectively, when performed 14 days or later after symptom onset, but sensitivity decreased at earlier time points. Immunoglobulin G developed rapidly and was sustained at high levels throughout follow-up (up to 58 days). Antibodies to SARS-CoV-2 predicted the odds of developing acute respiratory distress syndrome, which increased by 62% (CI, 48% to 81%; P< 0.001) for every 2-fold increase in IgG. Of 11066 NAAT-tested patients, 457 were repeatedly NAAT-negative, and serum samples were obtained for 18 such patients (6 COVID-19 case patients and 12 non-COVID-19 control patients). Antibodies were present in 5 of 6 case patients and none of the 12 control patients (P= 0.001). The study was retrospective and performed at a single center; the sample was small; follow-up was limited; and selection bias may have occurred. Antibodies to SARS-CoV-2 demonstrate infection when measured at least 14 days after symptom onset, are associated with clinical severity, and provide valuable diagnostic support in patients who test negative by NAAT but remain clinically suspicious for COVID-19. Clinical Immunology Laboratory, Department of Pathology, Johns Hopkins Hospital.

The role of toll-like receptor 9 (TLR9) in Epstein-Barr virus-associated gastric cancer

Abstract Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is the most common malignancy caused by EBV infection. Toll-like receptors (TLRs) as major components of innate immune system are crucial in the development of inflammatory processes and carcinogenesis. The aim of our study was to evaluate tissue and serum level of TLR9 in EBV-positive and EBV-negative gastric cancer patients. The study involved 30 EBV(+) and 30 EBV(-) patients. EBV DNA was detected in fresh frozen tumor tissue. In serum samples TLR9 level, transforming growth factor β (TGFβ), interleukin 10 (IL-10) and antibodies against EBV were detected using ELISA tests. TLR9 level was also measured in homogenate of tumour tissue. TLR9 level was statistically lower in EBV(+) patients both in serum and tissue, with statistically higher level in tissue than in serum. Lower level of TLR9 was accompanied by higher level of Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA). A lower level of TLR9 was detected in patients with poorly differentiated cancer (G3) and greater lymph nodes involvement (N3-N4). Lower level of TLR9 in patients with EA may point to TLR9 role in reactivation of EBV infection.

A soft metal-polyphenol capsule-based ultrasensitive immunoassay for electrochemical detection of Epstein-Barr (EB) virus infection

Herein, we have proposed a soft metal-phenolic capsule (sMPC)-based electrochemical immunoassay for ultrasensitive detection of Epstein-Barr virus capsid antigen IgA (EBVCA-IgA), a biomarker of nasopharyngeal carcinoma. Metal probes with large size contain a number of metal ions, which are very beneficial to signal amplification for anodic stripping voltammetry; however, these probes easily precipitate due to their heavy weight, leading to low recognition efficiency and compromised performance. In this study, we demonstrate sMPCs fabricated by metal-coordination interactions exhibit unique surface behavior compared with their solid counterparts, which significantly enhance recognition efficiency and thus improve sensitivity despite of their micrometer size. Taking advantage of the sMPCs, the involved electrochemical immunoassay shows a much-improved sensitivity with an ultralow detection limit of 0.46 fM for EBVCA-IgA and can also be used in real sample analysis. So far as we know, this is the first report on a sMPC-based electrochemical strategy. Furthermore, it clarifies the potential effect of the rigidness of probes on the performance of an involved biosensor, which is meaningful to guide the design of other functional probes. The advantages of this method, including easy to fabrication, ultrasensitivity and good selectivity, ensure a promising potential in the point-of-care diagnostics of critical diseases.

Clinical diagnostic criteria of efficiency for combined etiopathogenetic therapy in patients with chronic Epstein–Barr virus infection

Treatment of chronic viral infections accompanied by permanent virus persistence in the target epitopes of the oral cavity, skin, urogenital tract is complicated by virtual lack of available drugs exerting combined systemic virulicidal and immunomodulatory effects. Here we demonstrate clinical and immunological efficacy of combined therapy in treatment of Epstein–Barr virus (EBV)-associated chronic infections. The aim of the study was to evaluate the clinical and immunological efficacy of combined etiopathogenetic therapy using the Acegram cosmetic product in patients with EBV-associated chronic infections. Materials and methods. There were enrolled 40 patients monitored before treatment as well as 20 patients followed up after combination therapy (cycle therapy consisted of oral valaciclovir (Valtrex) applied at dose of 500 μg twice a day for 10 days, glucosaminylmuramyldipeptide (Licopid) — 10 mg 2 twice a day for 10 days, topical irrigation for mucous membranes with granulocyte-macrophage colony-stimulating factor active center-derived peptide (Acegram-spray) 3 times a day for 10 days. If necessary, treatment courses were repeated 20 days after the onset. All patients were examined for the presence of EBV genomes in the oral fluid and blood using the qualitative and quantitative polymerase chain reaction (PCR) using the DNA technology test system (Russia) on a DT-Lite device prior treatment and 30, 60 days post-therapy time points. In addition, serum samples were analyzed for level of class G immunoglobulins specific to the EBV nuclear and capsid antigens by using enzyme immunoassay (test systems manufactured by CJSC Vector Best, Russia) as well as immune status (clinical methods, enu flow cytometry evaluation of the phagocytic activity of neutrophils, ELISA method). Results. Use of single or two course combination therapy in subjects with fully eradicated EBV carriage associated with reversed clinical symptoms was accompanied by recovered immune system status (T and B cells, T-helper cells, CD3+ CD25+ cells, phagocytosis parameters). A non-invasive approach proposed for controlling virus elimination in the oral fluid by using polymerase chain reaction method may serve as to objectively monitor therapeutic efficacy.

Effects of Epstein-Barr Virus Infection on CD19+ B Lymphocytes in Patients with Immunorelated Pancytopenia.

Objectives To explore effects of Epstein-Barr virus (EBV) infection on CD19+ B lymphocytes in patients with immunorelated pancytopenia (IRP). Methods An enzyme-linked immunosorbent assay (ELISA) in vitro diagnostic kit was used to detect EBV capsid antigen- (CA-) IgG and VCA-IgM antibodies in the serum. We analyzed the EBV-DNA copies of CD19+ B lymphocyte by using real-time quantitative polymerase chain reaction (RT-qPCR). CD21, CD23, CD5, CD80, and CD86 receptors on the surfaces of CD19+ B cells were detected by flow cytometry (FCM). The correlation between these receptors and EBV-DNA copies were evaluated. Results The results revealed that the positive rate of EBVCA-IgM and CD19+ B lymphocyte EBV-DNA copy in the IRP group were significantly higher than those in the control group (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (Conclusions EBV infection may activate CD19+ B lymphocytes and further disrupt bone marrow hematopoiesis in IRP patients.

Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma.

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China.Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed.Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05).Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

Comparison of TGF-β, IL-10 levels and LMP-1 in gastric and oropharyngeal carcinoma associated with EBV infection

Abstract Increasing interest has been focused on the Epstein-Barr Virus (EBV)-associated cancers, including oropharyngeal cancer (OPC) and gastric cancer (GC). Different cytokines, growth factors and proteins take part in oncogenesis. The aim of our study was to generate a comparison of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels, as well as latent membrane protein (LMP-1), Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA) frequency in the serum of patients with GC and OPC. The study involved 50 patients with diagnosed GC and 50 patients with OPC. All studied patients were EBV positive. Fresh-frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. Sera from all individuals were investigated using ELISA tests to detect the presence of EBVCA IgG, EBNA IgG, EA IgG, as well as to determine the levels of IL-10 and TGF-β. The obtained results were subjected to statistical analysis. In patients with GC, the levels of TGF-β and IL-10 were significantly higher than in OPC patients. However, the frequency and level of EBVCA, EBNA and EA in patients with OPC and GC were not significantly different. In contrast, TGF-β and IL-10 levels were significantly higher in EBVaGC, as compared to OPC, suggesting their role in gastric carcinogenesis. The differences in frequency of LMP-1 detection in patients with OPC and GC may suggest different mechanism of oncogenesis. Further studies are required to clarify the role of Epstein-Barr virus in cancer development.

Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection.

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein‐Barr virus associated nasopharyngeal carcinoma

Exosomes have emerged as novel vehicles for proteins and other contents in cancer progression. Cyclophilin A (CYPA) is a pivotal member of immunophilin family. Whether CYPA can be detected in sera of nasopharyngeal carcinoma (NPC) patients remains to be explored. Epstein‐Barr virus (EBV) is the first identified human tumor virus and is a causative agent of NPC. The antibody of EBV capsid antigen immunoglobulin A (EBV‐VCA‐IgA) is a known biomarker of NPC, with a proportion of no more than 70% being detected positively. Hence, novel biomarkers need to be discovered for early diagnosis, prognosis, and monitoring of EBV‐associated NPC. A total of 110 NPC and 36 normal control serum samples were collected. Exosomes from these samples were extracted. The mRNA and protein expression levels of the above samples were validated by reverse transcription –quantitative polymerase chain reaction, Western blotting, or enzyme‐linked immunosorbent assay (ELISA). Finally, the results demonstrated that both the serum and exosomal CYPA levels of NPC patients were significantly higher than that of normal cases. In addition, exosomal CYPA had a much higher level than that in the whole sera. The positive rate of EBV‐VCA‐IgA antibody was 68.2% in NPC sera, and noticeably, among the cases with EBV‐VCA‐IgA negative, 80% of them presented high levels of CYPA above the standard (cutoff value). In particular, CYPA in exosomes was uniformly with higher significance than that in whole sera. Combined analysis of CYPA protein and EBV‐VCA‐IgA antibody showed a greatly higher discriminatory ability in diagnosis of NPC. Moreover, exosomal CYPA level had a positive correlation with that of the EBV‐encoded latent membrane protein 1 (LMP1) in exosomes. EBV‐positive cancer cells secreted significantly higher levels of exosomal CYPA. This study established the utility of circulating exosomal CYPA as a potential noninvasive diagnostic biomarker for EBV‐associated NPC.

S-S-PEG-COOH Self-Assembled Monolayer on Gold Surface Enabled a Combined Assay for Serological EBV Antibody Isotypes.

Epstein-Barr virus (EBV) is a ubiquitous human gamma herpes virus that infects human epithelial cells and B lymphocytes. It would be potentially valuable to develop novel combined assays to benefit screening for large panels of samples of EBV infectious diseases. A simple antigen-probed biochip that is modified with S-S-PEG-COOH and is used as a label-free high-throughput screening method for a combined detection of EBV capsid antigen IgM antibody, capsid antigen IgG antibody, and nuclear antigen IgG antibody. This protein biochip has similar feasibility, sensitivity, and specificity in comparison with Liaison chemiluminescent immunoassay (CLIA). Detection limit of the EBV antibodies by the biochip is almost identical to that by CLIA-L (2.91UmL-1 vs 3.00UmL-1 for EBNA-1 IgG, 8UmL-1 vs10UmL-1 for EBV-VCA IgG, and 3.5UmL-1 vs 10UmL-1 for EBV-VCA IgM). Tests of the three serological antibodies against EBV by the biochip are consistent with the CLIA-L method in 274 clinical sera, respectively. Finally, the combined biochip is successfully utilized for diagnostic identification of EBV infection in 14 patients with infectious mononucleosis (IM) and 25 patients with systemic lupus erythematosus SLE, as well as additional 10 known real-time PCR positive patients. This biochip format will enable concurrent detection of antibodies against EBV infection and confirm infection status of EBV. It will be a versatile tool for large-scale epidemiological screening in view of its miniaturization and high throughput.

Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors

Background. Viral infection is a major factor in virus-associated carcinogenesis.Objective: to evaluate the expression of growth factors and markers of apoptosis, proliferative activity, and angiogenesis in patients with viral DNA-positive bladder cancer.Materials and methods. The study included 100 bladder cancer patients (72 males and 28 females) aged between 38 and 90 years (mean age 65 ± 10). Tumor tissue samples were tested by polymerase chain reaction to detect DNA of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2 respectively), high-risk human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein—Barr virus (EBV). Immunohistochemical analysis was performed in 32 patients and included the following markers: proliferation marker Ki-67, p63, apoptosis regulator Bcl-2, p53, angiogenesis marker CD31, adhesion protein CD44, and epidermal growth factor receptor (EGFR).Results. Viral DNA in tumor tissue was detected in 34 patients; of them, 50 % had poorly-differentiated tumors. Twenty-seven patients were found to have EBV DNA in their tumor tissue; 6 patients had CMV DNA; 5 patients had high-risk HPV DNA (types 16, 39, 45, 52, and 59); 1 patient had HSV1 and HSV2 DNA. Four out of 34 participants had mixed infections (1 case of HPV 59 + EBV; 2 cases of EBV + CMV; 1 case of CMV + EBV + HPV 31 and 52). We observed a strong correlation between the presence of EBV DNA and levels of CD31 and Ki-67 expression as well as between high-risk HPV DNA and Bcl-2 expression. High levels of antibodies against EBV capsid antigen were associated with EGFR and Ki-67 expression, whereas the level of antibodies against EBV nuclear antigen correlated with CD44 expression. We evaluated specific characteristics of expression of the markers analyzed depending on the tumor stage, grade of anaplasia, and recurrence. We also assessed morphological characteristics of changes in lymphocytic and plasma cell infiltrates.Conclusion. We found a correlation between the presence of viral DNA in bladder cancer tissue and markers of proliferative activity, angiogenesis, and apoptosis. Viral infection is likely to increase proliferative activity and suppression of apoptosis, which may cause tumor progression. Further studies are needed to assess this correlation.

Assessment of the Long-term Diagnostic Performance of a New Serological Screening Scheme in Large-scale Nasopharyngeal Carcinoma Screening.

Background: Nasopharyngeal carcinoma (NPC) remains as a major public health burden in Southern China. Over the last decade, Epstein-Barr virus (EBV) serological detection has been the most promising tool used for NPC screening. The present study aims to evaluate the long-term diagnostic performance of a new NPC screening scheme (probability of NPC units [logit P], PROB≥0.65), and compare this with other EBV seromarkers used within 2009-2015.Methods: Enzyme-linked immunosorbent assay (ELISA) for EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA) was performed in 16,712 subjects, who were within 30-59 years old.All subjects were followed up for six years. The area under the receiver operating characteristic curve (AUC) and correlation analyses were preformed to evaluate the diagnostic value of different measures. Furthermore, the rates of early diagnosis in NPC patients were statistically analyzed.Results: The new NPC screening scheme (PROB≥0.65) and the four strategies (VCA/IgA, EBNA1/IgA, VCA/IgA and EBNA1/IgA, and VCA/IgA or EBNA1/IgA) had comparable rates of early diagnosis for NPC (no significant difference was found), but the sensitivity of the new scheme (95.7%) was higher than that of the others. The top three seromarkers with the largest AUC were PROB≥0.65 (AUC:0.926, 95% CI: 0.885-0.966), VCA/IgA or EBNA1/IgA (AUC:0.883, 95% CI:0.824-0.942), and EBNA1/IgA (AUC: 0.866, 95% CI: 0.794-0.938).Conclusion: The new NPC screening scheme (PROB≥0.65) based on VCA/IgA and EBNA1/IgA outperforms the other seromarkers, and making it the preferred serodiagnostic strategy for long-term NPC screening in high-incidence areas.

Cardiorespiratory fitness is associated with better control of latent herpesvirus infections in a large ethnically diverse community sample: Evidence from the Texas City Stress and Health Study

Regular exercise has been purported to improve immune function and prevent latent herpesvirus reactivation, which may help delay the onset of immunosenescence with advancing age. We determined the relationship between cardiorespiratory fitness (VO2max) and latent viral load in respondents of the Texas City Stress and Healthy Study (n = 1,455, 58.4 percent female; age 25–91 years). VO2max was estimated using non-exercise equations that incorporate physical activity rating, body-mass index, age and sex. VO2max was inversely associated with high serum antibody titers against the Epstein-Barr virus capsid antigen and cytomegalovirus (CMV) optical density (surrogate measure of viral load), withstanding adjustment for demographic variables (age, sex, race, education, income, smoking) and inflammation (IL-1; C-reactive protein). The VO2max and EBV relationship was strongest in Whites and Hispanics compared to Blacks, in women compared to men, and in those aged 65 years compared to those of younger age, but similar between men and women. VO2max was also inversely associated with high herpes simplex virus-1 antibody titers, but did not withstand adjustment for inflammation. We conclude that high levels of cardiorespiratory fitness are associated with better control of latent herpesvirus infections, advocating exercise as a viable behavioral intervention to offset age- related declines in immune function.

Multiple Evanescent White Dot Syndrome Following Acute Epstein-Barr Virus Infection

ABSTRACTPurpose: To investigate the association between multiple evanescent white dot syndrome (MEWDS) and Epstein-Barr (EB) virus infection.Methods: A prospective, consecutive case series study was performed in patients with the characteristic findings of MEWDS. Patients received EB viral-specific antibody serologic tests.Results: Five cases of MEWDS who had prodromal flu-like symptoms were enrolled, comprising 2 women and 3 men with a mean age of 34. Mean diopter of myopia was −7.5. During acute onset of MEWDS, EB virus infection was confirmed by positive EB virus serology test. One showed positive EB viral capsid antigen (EB-VCA) IgM, and the other four showed highly elevated titer of EB-VCA IgG more than 1:160. Two months later, paired serum virus serology data showed negative EB-VCA IgM, or prior EB-VCA IgG titer decreased four-fold in the recovery stage.Conclusion: MEWDS may be associated with acute systemic EB virus infection. Ocular symptoms might develop due to this infection or represent virus-induced autoimmune inflammatory retinitis.

Seroprevalence of cytomegalovirus in donors & opportunistic viral infections in liver transplant recipients.

Background & objectives:Opportunistic virus infections are common in liver transplant (LT) recipients. There is a risk of developing infection with cytomegalovirus (CMV) and herpes-related viruses such as herpes simplex virus-1 and 2 (HSV-1 & 2), Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV), reactivation of infection and recurrent infection. This study was conducted to determine CMV seropositivity in donors and its influence on LT recipients and seropositivity of CMV, HSV-1 and 2, EB viral capsid antigen (EBVCA) and VZV in LT recipients and their reactivation.Methods:Pre-transplant data for IgG and IgM for CMV (and donor), HSV-1 and -2, EB viral capsid antigen (VCA) and VZV were available for 153 recipients. All recipients were on ganciclovir or valganciclovir prophylaxis for three months after LT. For reactivation rates, findings of post-transplant CMV quantitative reverse transcription polymerase chain reaction (CMV qRT-PCR) assay were associated with pre-transplant serological profile.Results:Of the 153 LT recipients, 131 were men (85.6%). The median age of LT was 46 yr (range 9 months-71 yr). Overall exposure to CMV was 71.8 per cent followed by EB VCA (61.4%) and VZV (49.6%). Susceptibility to both HSV-1 and -2 was high across all decades (P<0.001). Seropositivity of CMV in donor was 90.9 per cent (100 out of 110). Post-transplant CMV qRT- PCR was positive in 17 (26.6%; 3 in recipient negative) of 64 samples tested. qRT-PCR assay was positive in one out of four (25%) tested for HSV-1 and nine out of 19 (47.4%) tested for EBV. Two recipients tested for HSV-2 and one for VZV were negative. There were three deaths in recipients (D+ R+) who were also positive for CMV qRT PCR. There was one death due to HSV-1 pneumonia. One patient with EBV reactivation developed post-transplant lymphoproliferative disorder two years after transplant.Interpretation & conclusions:Transplant recipient were at highest risk of acquiring HSV-1 and -2 more so for HSV-2. CMV exposure in transplant recipients and donors were very high and at greatest risk for recipient reactivation rate. Despite this, death related to CMV reactivation was low.

Diagnostic value of combined detection of serum DKK1 and EB virus VCA-IgA for nasopharyngeal carcinoma

Objective To explore the diagnostic value of the combined detection of serum Dickkopf-1(DKK1) and EB viral capsid antigen immunoglobulin A (VCA-IgA) in patients with nasopharyngeal carcinoma (NPC). Methods Serum levels of DKK1 and VCA-IgA were measured by enzyme-linked immunosorbent assay (ELISA) for the 80 patients with NPC and 65 normal controls. Receiver operating characteristic (ROC) curve was used to calculate the diagnostic value. Results The serum levels [M(QR)] of DKK1 in patients with NPC were significantly higher than those in normal controls [580.773(429.146)pg/ml vs. 316.174(252.965)pg/ml], with a significant difference (Z=4.846, P<0.000 1). ROC curves showed that the optimum diagnostic cutoff for serum DKK1 was 611.981 pg/ml, with an area under curve (AUC) of 0.734 (95%CI: 0.654-0.815, 50.0% sensitivity, 96.9% specificity). Measurement of VCA-IgA demonstrated an AUC of 0.714 (95%CI: 0.631-0.798, 47.5% sensitivity, 95.4% specificity). The combined detection of DKK1 and VCA-IgA demonstrated an AUC of 0.849 (95%CI: 0.783-0.914, 76.3% sensitivity, 95.4% specificity). For patients with early-stage NPC, the detection effect of combined detection of DKK1 and VCA-IgA was much better than that in normal controls, with a significant difference (χ2=23.784, P<0.001). Conclusion Serum DKK1 has potential diagnostic value for NPC. Combined detection of DKK1 and VCA-IgA may aid the early diagnosis of NPC. Key words: Nasopharyngeal neoplasms; Diagnosis; Dickkopf-1; EB viral capsid antigen immunoglo-bulin A

An unusual presentation of Epstein-Barr Virus induced hepatitis in a 15-month-old child

Objective: We report an atypical case of hepatitis in an infant that could be helpful to physicians of various specialties, as it demonstrates an atypical clinical and laboratorial manifestation of a disease not so common at that age and that could have gone undiagnosed. Case Description: A 15-month-old female, immunocompetent patient was referred to the hospital with a 3-day history of fever, vomiting, and diarrhea. The patient presented with alternation between sleepiness and irritation associated with rapid increase in serum liver enzymes levels, but no jaundice. Neurologic evaluation showed no meningeal signs and no encephalic morphological abnormalities were observed in a cranial CT scan. Treatment consisted of symptomatic medication and daily evaluation for signs of hepatic encephalopa- thy or bleeding. A serological panel showed negative IgM but positive IgG reactivity against Cytomega- lovirus (CMV) and IgM and IgG negative immunoreactivity against HAV. She was not tested for Hepatits B (HBV) or Hepatits C (HCV). Positive immunoreactivity against the Epstein-Barr virus capsid antigen (EBV VCA) IgM and negative reactivity against IgG, indicated a diagnosis of EBV-induced acute hepatitis. The patient was discharged asymptomatic after 11 days, with decreasing serum liver enzymes levels. A 15-day follow up evidenced complete remission of symptoms and normalized laboratory tests. Comments: Hepatic involvement in infections by Epstein-Barr Virus is common, presenting with moderate and transient increase in liver enzymes. It can go undetected and resolve spontaneously, while clinical manifestations of hepatitis are infrequent. In this report, we present an unusual case of a pediatric patient with hepatitis induced by EBV infection, along with a review of the literature. According to our search, no other EBV-induced hepatitis case reports have been published involving an immunocompetent patient under 2 years of age

Clinical characteristics of 73 children with Epstein-Barr virus encephalitis

Objective To summarize the clinical features of Epstein-Barr virus encephalitis(EBE), and to discuss the factors that could result in poor prognosis. Methods Seventy-three cases of EBE admitted to Beijing children′s Hospital, Capital Medical University from July 2006 to June 2016 were collected.The clinical features, laboratory tests and imaging results were analyzed, and the follow-up check-up by phone was conducted. Results EBE could occur at any time of the year, and more cases occurred in winter/spring than in summer/autumn.Ratio of male to female patients was 1.5∶1.0, and more cases occurred among the older children with their average age of 5 years and 6 months old.Specific types were: meningoencephalitis 56 cases(75.7%), demyelination 16 cases(21.9%), and acute cerebellar ataxia 1 case(1.4%). EBE included 24 cases (32.9%) of meningoencephalitis, 22 cases (30.1%) of encephalitis, 10 cases (14.0%) of meninges, 2 cases (2.7%) combined with myelitis, and 1 case (1.4%) combined with ophthalmoneuromyelitis.Only 2 cases were found with typical symptoms of infectious mononucleosis, 1 case was diagnosed as chronic Epstein-barr virus(EBV) infection, and 1 case was diagnosed as hemophagocytic histiocytosis.Clinical symptoms were: 70 cases (95.9%) of fever, 37 cases (50.7%) of convulsion, 34 cases (46.6%) of altered state of consciousness, 24 cases (32.9%) of vomit, and 21 cases (28.8%) of headache, which were found to be the primary symptoms, together with other symptoms, including 12 cases (16.4%) of hepatomegaly, 10 cases (13.7%) of rash, and 11 cases (15.0%) of other symptoms.There were 42 cases (57.5%) of central nervous system(CNS)infection positive and neck stiffness, 32 cases (43.8%) of Babinski′s sign positive, 10 cases (13.7%) of decreased muscle strength, 11 cases (15.1%) of atonia, 5 cases (6.8%) of hypermyotonia, 5 cases (6.8%) of coats disease positive, and 2 cases (2.7%) with Brudzinski signs.Twenty-two patients (30.1%) did not have CNS positive symptoms.There were 48 cases (45.8%) of magnetic resonance imaging (MRI) result showing abnormalities, with common symptoms including 9 cases (12.7%) of cytotoxic edema, 8 cases (11.3%) of demyelination, and 4 cases (5.6%) with encephalanalosis symptoms.Affected organs included 14 cases (19.7%) of frontal lobe, 11 cases (15.5%) of parietal lobe, 11 cases (15.5%) of temporal lobe, 8 cases (11.3%) of thalamus, 7 cases (9.9%) of basal ganglia, 6 cases (8.5%) of occipital, and 5 cases (7.0%) of corpus callosum etc.Follow-up check-up was conducted on 52 cases, with 21 cases lost contact, and 44 cases (84.6%) with good prognosis, 8 cases (15.4%) with poor prognosis and 3 death cases (5.8%). Serologic examinations found 20 cases (29.9%) of primary EBV infection [EBV-capsid antigen(CA)-IgM+ and core antigen(NA)-IgG-], 47 cases (70.1%) of existed EBV infection being activated (EBV-CA-IgM+ and NA-IgG+ ), and there was no statistically significant difference in terms of clinical characteristics and prognosis.Convulsion occurs more frequently in group of poor prognosis(P=0.03) after comparing the aspects of main clinical features, stage of EBV infection, underlying diseases and combined with other infections etc(P>0.001). Conclusions EBE can occur at various stage of EB infection.EBE can occur in various forms at clinic.CNS symptoms of meningoencephalitis, encephalitis, meninges, demyelination, and cerebellar ataxia etc.Patients’ brain parenchyma can be affected extensively, and most of the patients experienced good prognosis, the virus can cause lethal infection; while patients with symptoms of convulsion may experience poor prognosis. Key words: Epstein-Barr virus; Encephalitis; Child

Analysis of clinical features of 21 cases of adult infectious mononucleosis

Objective To improve understanding of infectious mononucleosis by reporting the clinical data of 21 adults diagnosed as infectious mononucleosis. Methods We investigated retrospectively the clinical and laboratory data of 21 patients diagnosed as infectious mononucleosis. Results Among those 21 cases, the manifestations were fever(19 cases, 90%), angina(14 cases, 67%), lymphadenopathy(15cases, 71%), hepatosplenomegaly (9 cases, 43%). Laboratory results showed that increased leucocyte count(10 cases, 48%), high percentage of abnormal lymphocytes between 10% to 29%(14 cases, 67%), abnormal liver function(18 cases, 86%), positive Epstein-Barr virus capsid antigen IgM(18 cases, 86%). All 21 patients were get better. Conclusion It showed that the clinical manifestations of infectious mononucleosis in adults were complex and diverse.The diagnosis should be combined with clinical manifestations and relevant examination.The outcome of this disease is good. Key words: Infectious mononucleosis; Aged