EBV Antibody Research Articles

S2614 Cholestatic Hepatitis From Acute Epstein-Barr Virus Infection

INTRODUCTION: Primary Epstein-Barr Virus infection (EBV) presents as a triad of fever, posterior lymphadenopathy and pharyngitis. Hepatocellular involvement is limited to transient, mild, asymptomatic elevations of aminotransferases. Clinical manifestations of hepatitis are rarely the presenting feature of the disease and severe cholestasis is exceedingly rare. We present a patient with atypical presenting features found to have cholestatic hepatitis due to acute EBV infection. CASE DESCRIPTION/METHODS: A 38-year-old male with no medical history presented with right upper quadrant (RUQ) abdominal pain for 1 week associated with malaise, dyspnea, nausea, emesis, and fever to 38.8 degrees Celsius. His social history consisted of safe sex practices, no sick contacts, and no drug or alcohol use. On examination, he was afebrile and hemodynamically stable. There was no jaundice, scleral icterus or lymphadenopathy. There was mild tonsillar erythema without edema or exudate. He had RUQ and epigastric tenderness to palpation without notable hepatosplenomegaly. His labs showed no leukocytosis with elevated aspartate aminotransferase (AST) 234 IU/L, alanine aminotransferase (ALT) 383 IU/L, alkaline phosphatase 432 IU/L, and total and direct bilirubin of 3.4 and 1.6 mg/dL, respectively. ALT and AST peaked at 743 and 582 IU/L, respectively. HIV and hepatitis panel were negative. RUQ ultrasound showed normal gallbladder (GB) wall thickness of 2.7 mm with mild distention, trace pericholecystic fluid, and no biliary dilation. Magnetic resonance cholangiopancreatography showed mild hepatosplenomegaly, a normal GB and no biliary obstruction. Further workup revealed a positive Monospot with >160 units/ml of EBV antibodies to viral capsid antigen IgM and indeterminate EBV antibody to viral capsid antigen IgG, indicating acute EBV infection. DISCUSSION: EBV cholestasis is thought to be secondary to inflammation of the bile duct and direct damage to hepatic cells by autoantibody-mediated activation of free radicals. A literature review revealed that EBV has been reported to cause a hepatocellular pattern of elevated aminotransferases however cholestatic patterns are infrequently reported and thus may cause a diagnostic dilemma. The existing literature reports this phenomenon in pediatrics, adolescents, or patients in the second decade of life. Our case highlights the importance of including EBV infection in the differential diagnosis of cholestatic hepatitis at any age, particularly when no demonstrable cholecystitis is present.Table 1.: Liver and biliary marker trend throughout hospitalizationFigure 1.: Abdominal MRI demonstrating hepatomegaly and splenomegaly, measuring 15.1 cm anterior-posteriorly, and 13.9 cm craniocaudally.Figure 2.: Abdominal MRI demonstrating hepatosplenomegaly.

Clinicopathological and prognostic features of nasopharyngeal carcinoma in children and adolescents: A retrospective study of 196 cases in South China.

Nasopharyngeal carcinoma (NPC) occurring in children and adolescence is extremely rare and till present there is a lack of understanding on their clinicopathological and prognostic features of this rare entity. For our study, data of 196 cases children and adolescents with NPC from the past 18 years at a high-volume cancer center from South China were retrospectively analyzed. Half of the evaluated NPC patients (83/166, 50.0%) were staged as Stage IVa disease, whereas 1.2% (2/166), 27.7% (46/166), 16.9% (28/166) and 4.2% (7/166) had Stage II, III, IVb and IVc disease, respectively. Serum EBV EA-IgA ≥1:10 and VCA-IgA ≥1:40 were found in 67.7% (113/167) and 76.6% (128/167) of the evaluated patients, respectively, whereas 56.8% (84/148) of the patients had plasma EBV DNA ≥1000 copies/mL. Histologically, all tumors were classified as nonkeratinizing squamous cell carcinoma (NK-SCC). Immunohistochemistrically, the expression of CK (AE1/AE3), P63, CK5/6 and P40 were observed in 100% (88/88), 93.2% (68/73), 84.1% (58/69) and 63.2% (12/19) of the detected cases, respectively. All cases show similar immunophenotype compared to that occurring in adult patients. All evaluated cases (71/71 100%) harbored EBER. Patients with plasma EBV DNA ≥1000 copies/mL and positive serum EBV antibodies had significantly inferior 3-year OS (88% vs 100%, P = .007) compared to other corresponding groups. The combination of EBV serology and plasma EBV DNA are useful to predict the outcome of patients with NPC in children and adolescents.

Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study

BackgroundHashimoto’s thyroiditis (HT) is now considered one of the most prevalent autoimmune diseases. The aim of the present study was to determine the prevalence of different types of EBV antibodies in patients with HT in comparison to healthy controls, and to detect any correlation between EBV serological markers and different laboratory findings in HT patients. Subjects & methodsThis case-control study was conducted on 120 subjects divided into two groups: Sixty patients with HT (patients group), and sixty age and sex matched healthy volunteers (control group). All the participants were subjected to: Thyroid ultrasound, laboratory assessment including: Serum thyroid -stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase antibody (anti-TPO Ab) and anti-thyroglobulin antibody (anti-TG Ab). Four types of EBV antibodies (VCA IgM, VCA IgG, EA IgG, and EBNA-1IgG) were measured in serum using ELISA. ResultsThe mean serum levels of EBV VCA IgG and EA IgG were significantly higher in HT patients group in comparison to control group. In euthyroid HT patients, a significant positive correlation was observed between the age and EBV EA IgG. While in hypothyroid HT patients, a significant positive correlation between thyroid isthmus and EBNA-1IgG was observed. A significant negative correlation was found between the serum FT3 and EBNA-1IgG and a significant positive correlation was observed between serum TSH and EBV VCA IgG. ConclusionsThe high serum levels of EBV VCA IgG and EBV EA IgG in patients with HT suggest a possible association between EBV and HT.

Development of an Improved Epstein-Barr Virus (EBV) Neutralizing Antibody Assay to Facilitate Development of a Prophylactic gp350-Subunit EBV Vaccine.

No licensed vaccine is available for prevention of EBV-associated diseases, and robust, high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate EBV vaccines. Here we have developed an improved EBV-GFP based neutralization assay for such a vaccine’s pre-clinical and clinical validation to measure EBV specific neutralizing antibodies in human donors. The supplementation of guinea pig complement of our previously published high-throughput EBV-GFP fluorescent focus (FFA)-based neutralization assay allowed the detection of complement-dependent neutralizing antibodies using a panel of heat-inactivated healthy human sera. Anti-gp350 antibody titers, which were evaluated using a previously optimized anti-gp350 IgG ELISA assay, were moderately correlated to the FFA-based neutralization titers. Overall, this improved high-throughput neutralization assay is capable of characterizing the serologic neutralizing antibody response to natural EBV infection, with applications in evaluating EBV antibody status in epidemiologic studies and immunogenicity of candidate gp350-subunit EBV vaccines in clinical studies.

Combination of serum matrix metalloproteinase-3 activity and EBV antibodies improves the diagnostic performance of nasopharyngeal carcinoma.

Objective: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor that is highly prevalent in Southeast Asia. The two traditional NPC markers VCA-IgA (EBV viral capsid antigen) and EA-IgA (EBV early antigen) are limited in the screening and diagnosis of NPC. The purpose of present study is to evaluate the diagnostic value of matrix metalloproteinase-3 (MMP3) in NPC.Methods: The levels of 23 secretory MMPs in serum samples from 15 healthy controls and 26 NPC patients were detected by Cytokine Antibody Array 2000. Immunohistochemistry, Real-time PCR and western bolt were used to detect MMP3 mRNA and protein levels in NPC tissues and cell lines. The serum protein levels of MMP3 were further measured by ELISA in healthy control individuals (n = 200) and NPC patients (n = 206).Results: MMP3 can be expressed and secreted by both NPC and fibroblast cell lines, suggesting that the higher expression of MMP3 protein in both tumor nests and stromal of NPC tissues may be the source of circulating MMP3 in NPC patients. Furthermore, we found out both MMP3 concentration and enzymatic activity were significantly increased in the NPC group (n = 206) than the healthy control group (n = 200) (P < 0.001). However, serum MMP3 enzymatic activity, but not MMP3 concentration, was significantly associated with the progression of NPC. In addition, serum MMP3 activity was more valuable in diagnosis of NPC than its concentration (0.86 vs. 0.78, AUC), and MMP3 activity can improve the diagnosis of NPC by combining with EBV-infection biomarkers VCA-IgA and EA-IgA with a sensitivity of 91.5% and a specificity of 92.3%.Conclusions: This study suggested the combination of MMP3 activity and EBV antibodies may be a useful biomarker for screening and diagnosis of NPC.

Predictors of Epstein-Barr virus serostatus in young people in England

BackgroundEpstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies.MethodsThe Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection.ResultsDemographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11–14 year olds throughout adolescence (68.6% in 15–18 year olds) and stabilising by early adulthood (93.0% in those aged 22–24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13–4.78]). Smoking was less strongly associated with EBV seropositivity.ConclusionsBy the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies.

2359 Acute Liver Failure in the Setting of HSV-Induced Hemophagocytic Lymphohistiocytosis

INTRODUCTION: Acute liver failure (ALF) is characterized by acute (&lt; 26 weeks) liver injury, encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without a preexisting liver disease carries a poor prognosis1. Common etiologies of ALF include acetaminophen toxicity, sepsis, and toxin exposure2. Here, we present a rare case of ALF secondary to HSV-induced Hemophagocytic lymphohistiocytosis (HLH). CASE DESCRIPTION/METHODS: A 57-year old male with a history of hypertension presented with a week history of cough and fever. Review of systems also included fatigue, decreased appetite, and decreased interactiveness. Labs were remarkable for anemia, thrombocytopenia (plt 15,000), tranaminitis (AST/ALT 6943/1551), ferritinemia (&gt;105,000 ng/mL) and hypofibrinogenemia (134 mg/dL). Workup for causes of ALF was unrevealing, including acetaminophen, viral hepatitis, Wilson Disease, and autoimmune hepatitis. Blood and urine cultures, respiratory viral PCR, Adenovirus PCR, HIV Ab/Ag, Lyme IgM/IgG, ANA and RF were negative. HSV and EBV antibodies were collected early in admission. A CT Chest was unremarkable and a CT abdomen showed diffuse hepatic hypo-attenuation. His course was complicated by hypothermia, hypotension, and unresponsiveness prompting intubation and admission into the ICU. He was started on broad spectrum antibiotics as well as high dose steroids. His clinical status continued to deteriorate after-which his family requested comfort care measures. Postmortem autopsy demonstrated hepatomegaly with HSV hemorrhagic and necrotic hepatitis resulting in confluent non-zonal hepatic necrosis, as well as splenomegaly. Postmortem his HSV IgM (type 1 and 2) was not detected. His serum EBV IgM and IgG elevated with PCR showing 2246 copies/mL. DISCUSSION: This was a case of ALF due to suspected HSV-induced HLH. In review of the literature, only one other case study has reported ALF in the setting of HSV-induced HLH3. The diagnosis of HLH clinically requires 5/8 criteria [Table 1]4. Our patient met five of eight criteria for HLH. Notably, both EBV and HSV have been strongly implicated as potential triggers for HLH5. Although primary liver disease and HLH can present in a similar fashion, HLH tends to incorporate more extensive organ involvement, cytopenias, extremely high ferritin, and neurologic findings. Our case a rare precipitating cause of ALF, highlighting the importance of considering HSV-induced HLH early in the course of newly diagnosed ALF given their rapid deterioration.

Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein-Barr Virus: An analysis of a prospective study in southern China.

BackgroundThe association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design.MethodsA NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE).ResultsWith a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE.ConclusionSmoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV.

Effect of cetuximab on development of viral infectious complications in laryngeal cancer.

e17578 Background: Cytostatic treatment was shown to influence significantly reactivation of latent viral infections. Our purpose was to study the possible effect of cetuximab on activation of herpesvirus infections. Methods: The blood serum of patients with histologically confirmed laryngeal squamous cell carcinoma was studied before and after chemotherapy. The main group included 9 pts receiving cetuximab+cisplatin+5-fluorouracil, the control group – 9 pts, cisplatin+5-fluorouracil. Antibodies (AB) against viral proteins were detected by ELISA. Results: 6 (66.7%) pts of the main group had primary advanced cancer, 3 (33.7%) – recurrent laryngeal cancer; in control group - 7 (77.7%) and 2 (22.2%), respectively. All pts in both groups were seropositive for HSV 1,2, CMV and EBV before chemotherapy; 4 (44.4%) pts in main group and 7 (77.8%) controls were HPV 6 seropositive. Serological markers of activation of herpes virus infection (IgM or IgG against early viral proteins) after chemotherapy were detected in the main group in 8 (88.9%): HSV 1,2 - 5 (55.6%), CMV - 2 (22.2%), EBV - 3 (33.3%). HSV 1,2, CMV and EBV infections in the control group were activated equally often and found in 3 (33.3%) pts. Clinical signs of herpes virus infection were not observed in either group. A sharp decline in AB titers, sometimes up to their complete disappearance, was registered in 3 (33.3%) pts in the main group and in 6 (66.7%) controls. 1 pt of the main group showed a decline in EBV AB titers and absence of HPV 6 AB titers, 1 pt - a decline in CMV and EBV AB, 1 pt - a decline in HSV 1,2, CMV and EBV AB and absence of HPV 6 AB titers. 2 pts of the control group showed a decrease in HPV 6 AB, 2 pts – their absence, 2 pts – absence of HPV 6 AB and a decline in HSV 1,2, CMV and EBV AB. It could be associated with a greater degree of bone marrow hematopoiesis inhibition during cytostatic therapy. Lymphopenia was registered in the control group more frequently than in the main one. Conclusions: Cetuximab inclusion into chemotherapy does not have an additional negative impact on the development of viral infectious complications. A higher rate of registration of specific antibodies typical of the acute infection phase in the cetuximab group could indicate an adequate response to viral infection.

The value of plasma EBV-DNA testing in high-risk group of nasopharyngeal carcinoma in the nasal endoscopy

Objective:The aim of this study is to evaluate the level of plasma EBV DNA and nasal endoscopy in high risk population of nasopharyngeal carcinoma, and to explore the value of EBV DNA testing in nasal endoscopy. Method:The nasopharyngeal carcinoma was screened in High-incidence Area of Zhongshan City. EBV antibody was detected by ELISA, and 427 patients with high risk of nasopharyngeal carcinoma were identified. In the high risk population the plasma EBV-DNA was measured using Fluorescent quantitative PCR, and all patients were used nasal endoscopy in the first two years. The application value of EBV DNA and nasopharyngeal endoscopic biopsy were analyzed. Result:There were 427 NPC high risk population in first screening. The rates of nasopharyngeal biopsy in EBV DNA positive and EBV DNA negative population were 90.2% (55/61) and 13.9% (51/366), respectively. The rate of NPC nasopharyngeal biopsy in EBV DNA positive population was higher than that in EBV DNA negative population (P<0.01). The rate of NPC detection in EBV DNA positive group (60.7%) was higher than that (3.3%) in EBV DNA negative population (P<0.01). In first year follow up, there were 286 NPC high risk population. The rates of nasopharyngeal biopsy in EBV DNA positive and EBV DNA negative population were 91.2% (31/34) and 11.9% (30/252), respectively. The rate of NPC nasopharyngeal biopsy in EBV DNA positive population was higher than that in EBV DNA negative population (P<0.01). The rate of NPC detection in EBV DNA positive group (17.6%) was higher than that (1.6%) in EBV DNA negative population (P<0.01). The positive predicative value of serological risk assessment was 8.3% (59/713), but for NPC high risk group, adding quantitative analysis of plasma EBV DNA, the positive predicative value was 45.3% (43/95). The early diagnosis rates in EBV DNA positive and EBV DNA negative population were 79.1% (34/43) and 93.8% (15/16), respectively. There was no significant difference in early diagnosis rates in two groups (P>0.05). Conclusion:The positive rate of plasma EBV DNA in high risk group of nasopharyngeal carcinoma may be helpful for nasal endoscopic nasopharyngeal biopsy, which can greatly improve the positive predictive value of high risk population of nasopharyngeal carcinoma. For NPC high risk population, Therefore, EBV DNA positive population are the focus for NPC screening.

EBV-Associated T-Cell Lymphoproliferative Diseases in Young Adults with Unusual Histopathological and Immunophenotypic Features

EBV-associated T-cell lymphoproliferative diseases (EBV T-cell LPDs) in non-immunocompromised hosts are a heterogenous syndrome which is challengeable for both diagnosis and treatment. Here, we report four young patients of EBV T-cell LPDs with unusual histopathological and immunophenotypic features. They presented with intermittent high fever (4/4), multiple lymphadenopathy (4/4), hepatosplenomegaly (4/4), hematochezia (2/4) and high blood EBV antibodies titer (4/4) for seven months to one year. The enteroscopic examination revealed multiple ileocecus ulcers in three of four cases. Histologically, three cases showed similar dense infiltration of polymorphic composition including variable reactive components such as plasma cells and histiocytes as well as atypical lymphocytes and one case was characterized by proliferation of monomorphic atypical lymphocytes. The infiltrating lymphocytes were medium-sized with hyperchromatic nuclei and showed mild cytologic atypia. Abundant eosinophils infiltration and formation of eosinophilic abscess were seen in all cases. Multiple foci of necrosis with granuloma were observed in lymph nodes of all cases, but hemophagocytosis was absent. The immunohistochemical staining showed that infiltrative lymphocytes were CD2 TIA1 CD56﹣, suggesting cytotoxic T-cells origin, but loss of pan-T markers CD3 (2/4), CD5 (4/4) and CD7 (2/4) were frequently observed. Negativity for both CD4 and CD8 (4/4) and silent T-cell receptor (TCR) expression (3/3) were detected. EBV positivity in numerous T-cells was identified by double staining of CD3 and EBER. Three patients died within one year and one patient is alive six months after initial presentation. These unusual pathologic findings prompt us being aware of EBV T-cell LPDs and add to the understanding of this rare disease.

Viral serological and molecular data on possible involvement of herpes viruses in periodontal disease

BackgroundRecent studies have suggested that latent herpes virus infections can be associated with chronic periodontal sites that exhibit a predisposition to disease progression.The aim of this study was to identify the possible relationship between infections with CMV and EBV and the severity of periodontal disease. Materials and methodsFifty two patients aged between 27 and 70 years, diagnosed with periodontal disease were enrolled in the study after giving informed consent. Quantitative immunoenzymatic assays were used to determine the concentration of anti CMV and EBV antibodies. The presence of CMV and EBV DNA was tested in biopsies from periodontal tissues using an in-house PCR adapted after a method described previously. Results and conclusionsHigher titers of the anti CMV antibodies appear to be correlated with the severity of the periodontal lesions (p<0, 05). These correlations have not been found for anti EBV antibodies. Higher titers of specific anti CMV and EBV antibodies were correlated with a history of periodontal treatment (p<0, 05). Only two samples were positive for the viral genome. Both samples were collected from female patients diagnosed with very advanced forms of periodontal disease.Although the molecular biology data from the present study do not support the pathogenic involvement of EBV or CMV in the development of chronic periodontitis lesions, the serological data might be important markers for the evolution and severity of the periodontal disease

Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

Evaluation of the abbot Architect™ epstein-barr virus viral capsid antigen IgM, viral capsid antigen IgG and nuclear antigen IgG assays in a pediatric and adult population

BackgroundThe detection of antibodies against Epstein-Barr viral capsid (VCA) and nuclear (EBNA) antigens is routinely performed with different commercially available immunoassays. ObjectivesIn this study, we evaluated the concordance and performance of the Architect™ chemiluminescent microparticle immunoassays (CMIAs) using Captia™ enzyme linked immunosorbent assays (ELISA) for VCA IgM, and standard immunofluorescence (IF) assays for VCA IgG and EBNA IgG as comparative techniques. Study designSera were selected from a heterogeneous population including pediatric and adult patients. ResultsConcordance between CMIAs and comparative assays was high with total agreement percentages of 84,1% (95% CI: 77.8–88.9) for VCA IgM, 90,6% (95% CI: 84.2–94.7) for EBNA IgG and 98,0% (95% CI: 93.9–99.6) for VCA IgG. Moreover, kappa statistic values showed good to excellent correlation with values of 0.68 (95% CI: 0.57–0.79) for VCA IgM, 0.73 (95% CI: 0.58–0.87) for EBNA IgG and 0.95 (95% CI: 0.89–1.00) for VCA IgG. A correlation was observed between positivity levels on CMIAs and semi-quantitative fluorescence intensity on IF for VCA IgG and EBNA IgG assays. With regard to an accepted gold standard IF assays, CMIA was 98,1% (95% CI: 93.3–99.8) sensitive and 97,4% (95% CI: 86.5–99.9) specific for the detection of VCA IgG. For the detection of EBNA IgG, it was 92,2% (95% CI: 85.1–96.6) sensitive and 84,6% (95% CI: 65.1–95.6) specific. ConclusionIn summary, we demonstrated that the CMIA EBV antibody detection panel has high performance and high concordance with other commercially available immunoassays.

Hepatitis B virus infection and risk of nasopharyngeal carcinoma in southern China.

Whether or not hepatitis B virus (HBV) infection plays a role in the development of nasopharyngeal carcinoma (NPC) is largely unknown. Our study aimed to assess the association between HBV infection and the risk of NPC in Southern China. We conducted a case-control study including 711 NPC cases and two groups of controls. The first control group consisted of 656 individuals with other benign tumors unrelated to HBV infection and the second group consisted of 680 healthy population controls. Multivariable ORs and corresponding 95% confidence intervals (CI) for NPC were estimated by logistic regression. Patients with NPC had higher prevalence of antibodies against hepatitis B core antigen-positive [anti-HBc-(+); 47.26%] compared with either benign tumor controls (39.33%; P < 0.01) or healthy controls (41.18%; P = 0.04). In multivariable models adjusting for a set of risk factors for NPC, anti-HBc-(+) was significantly associated with a higher risk of NPC [adjusted OR (AOR), 1.40; 95% CI, 1.12-1.74 compared with the benign tumor controls and AOR, 1.48; 95% CI, 1.05-2.08 compared with the healthy controls]. The association was not modified by hepatitis B surface antigen (HBsAg) status. Finally, compared with the healthy controls, individuals with both anti-HBc-(+) and EBV antibodies had largely increased risk of NPC (AOR, 141.82; 95% CI, 68.73-292.62). Our study suggests that HBV infection is associated with NPC risk in Southern China. Prevention for HBV infection may play a role in the development of NPC.

High expression of XPA confers poor prognosis for nasopharyngeal carcinoma patients treated with platinum-based chemoradiotherapy.

In this study, we tried to explore if xeroderma pigmentosum complementation group-A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future.

Gender influence in EBV antibody response in multiple sclerosis patients from Kuwait

BackgroundEpstein–Barr virus (EBV) infection is implicated with multiple sclerosis (MS) risk, exacerbation, and progression. The HLA-DRB1*1501 haplotype is a strong MS risk factor consistently documented in MS populations. There are no studies of EBV infections and HLA-DRB1*1501 haplotype associating with MS from Kuwait where MS prevalence has increased significantly. ObjectivesTo determine the association of EBV infection with MS incidence, and to investigate HLA-DRB1*1501 as a potential genetic risk factor for MS in Kuwait. MethodsThis is a case–control study involving 141 MS patients and 40 healthy controls. Antibody titers against EBV antigens' viral capsid antigen (VCA) and Epstein–Barr nuclear antigen 1 (EBNA1) were measured using enzyme-linked immunosorbent assays. HLA-DRB1*1501 haplotype assessment was done using rs3135005 TaqMan genotyping assay. ResultsAntibody titers against EBV were significantly elevated in MS patients compared to healthy controls (anti-EBNA1, p=0.008; anti-VCA, p=0.028). MS males had higher antibody titers to EBNA1 than healthy male controls (p=0.005) and female MS patients (p=0.03). HLA-DRB1*1501 haplotype genotypes failed to generate a risk association with MS or EBV antibody titers (p=0.6). ConclusionAn increased immune response to EBV infection is associated with MS incidence influenced by the type of antigen and sex. HLA-DRB1*1501 haplotype is not associated with MS risk in our Kuwaiti MS cohort.

EBV Encephalitis in Acute Infectious Mononucleosis

Case Study: A 9-year-old boy was admitted to our hospital after an epileptical seizure. He presented with a 6-day history of fever and general body aches. On clinical examination, he was found to have a tonsillitis and swollen cervical lymph nodes. Because of a decreasing vigilance, a lumbar puncture was performed 16 hours after admission. The analysis of cerebrospinal fluid (CSF) showed an increased cell count of 115/µL. We then started a therapy with aciclovir and cefotaxim. Because of inadequate improvement, an MRI scan was performed 32 hours after admission, which was seen as normal by the pediatric radiologists. The situation of the patient worsened further with decreasing consciousness and cerebral seizures, which could not be managed by levetiracetam. Overall, 72 hours after admission, he was transferred to the intensive care unit, intubated and anesthetized with thiopental. Suspecting a Epstein-Barr virus encephalitis, DD an Autoimmune Encephalitis another lumbar puncture was performed and a therapy with glucocorticoids was started. After positive EBV specific PCR on CSF and confirmed intrathecal EBV antibody production intravenous immunoglobulins were added for 3 days. With this therapy, the condition of the patient improved. He was extubated after 6 days and was discharged with only slight cognitive and motoric restrictions for rehabilitation after 3 weeks. In retrospective the initial MRI, in comparison to a follow-up MRI, showed a symmetrical hyperintensity of gray matter as well as a moderate compression of the ventricles, which are typical for the acute stage of EBV encephalitis.

Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study.

BackgroundEpstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia.MethodsInformation on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models.ResultsAlmost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers.ConclusionsHighly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia.Electronic supplementary materialThe online version of this article (doi:10.1186/1750-9378-10-5) contains supplementary material, which is available to authorized users.

Nasopharyngeal and CNS-PTLD after heart transplantation in a 3 year old boy: Successful remission after haploident EBNA1 specific activated T-Cell transfers

Post transplantation lymphoproliferative disease (PTLD) is a rare and often fatal lymphoma. It occurs especially in children after solid organ transplantation. We report about a 3-year-old boy who underwent heart transplantation (HTX) at the age of 2 ½ years due to severe coronary artery stenoses after Kawasaki’s disease. After successful HTX he contracted primary EBV infection with chronification and CNS affliction. Despite treatment with rituximab, ganciclovir and lowering of immunospuppression, EBV infection triggered nasopharyngeal and CNS PTLD, visible on MRI and PET-CT. Clinically, fever, inspiratory stridor, mucositis, stupor and ataxia were noted. EBV specific T-cells or antibodies could not be detected. Upon rapid clinical deterioration, father and grandmother were identified as haploident T-cell donors. Transfer of EBNA1 activated T-cells was performed three times. EBV viral load, clinical symptoms and foci on MRI and PET-CT resolved. The boy has remained in remission for 12 months now.