Viral Capsid Antigen Immunoglobulin Research Articles

Intrathecal production of anti-Epstein-Barr virus viral capsid antigen IgG is associated with neurocognition and tau proteins in people with HIV.

HIV and Epstein-Barr virus (EBV) co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH). Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy ( n = 70) or not. Serum and CSF anti-EBV viral capsid antigen immunoglobulin G (anti-EVI) and CSF EBV DNA were measured by commercial immunoassay and RT-PCR. Seventy-eight participants without neurological confounding factors underwent neurocognitive assessment (Global Deficit Score, GDS). CSF total tau and 181-phosphorylated-tau (ptau) were measured by immunoassays together with biomarkers of blood-brain barrier (BBB) integrity, immune activation, astrocytosis, and intrathecal synthesis. Logistic and linear regressions and moderation analysis were used to investigate the relationships between CSF anti-EVI, GDS, and biomarkers. Twenty-one (17.1%) and 22 participants (17.9%) had detectable CSF anti-EVI (10.5-416.0 U/ml) and CSF EBV DNA (25-971 copies/ml). After adjusting for BBB integrity, age, and clinical factors, the presence of CSF anti-EVI was only associated with serum levels of anti-EVI, and not with CSF EBV DNA. CSF anti-EVI, tau and ptau showed reciprocal interactions affecting their associations with GDS. After adjusting for demographics and clinical parameters, higher CSF anti-EVI levels were associated with worse GDS (aβ 0.45, P < 0.001), and CSF levels of tau and ptau had a moderation effect on the strength of this association (models' P < 0.001). Humoral immune responses against EBV within the central nervous system may contribute to NCI in PWH through mechanisms that involve neuronal injury.

EBV antibody and gastric cancer risk: a population-based nested case-control study in southern China

BackgroundWe aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk.MethodsWe analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs).ResultsAll the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26).ConclusionsOur research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed.

Cholestatic Hepatitis Secondary to Epstein–Barr Virus Infection in Children: Case Series and Review of the Literature

Abstract Objective Cholestatic hepatitis (CH) secondary to Epstein–Barr virus (EBV) infection is a rare clinical condition in children and adolescents, which was reported in 5% of patients. Herein, we aimed to present our pediatric cases of EBV-induced CH with a comprehensive review of previously reported patients. Methods Three cases of EBV-induced CH diagnosed in our department were included in the study. EBV diagnosis was established with positive viral capsid antigen immunoglobulin M and immunoglobulin G. A search of English literature on pediatric cases with EBV-induced CH was conducted on common search engines (PubMed and GoogleScholar). Results We report three novel cases (aged 6, 15, and 16 years) presented with infectious mononucleosis and jaundice. The physical examination revealed mild hepatomegaly in all of them. In our cases, a total of 21 pediatric patients with EBV-induced CH were reported until now (52.4% male), with a median age of 15 (1–18) years. Regarding all patients, the most common symptoms were fever (94.1%) and jaundice (84.6%). In laboratory results, aspartate aminotransferase [308 (62–2,148) IU/L], alanine aminotransferase [312 (79–899) IU/L], and γ-glutamyl transpeptidase [328.9 ± 198.6 IU/L] levels were elevated. Hyperbilirubinaemia was observed in all cases with a median direct bilirubin level of 3.9 (1.9–21.8) mg/dL. A thickened gallbladder wall was the most common (50%) finding in the abdominal ultrasonography of the cases. Most of the reported patients recovered under supportive treatment without any further morbidity. Conclusions Although EBV-induced CH is an atypical presentation for children, it should be considered in the differential diagnosis of cholestasis. Supportive therapies are the mainstay of treatment in most of these cases.

Anti-EBNA1 IgG titre is not associated with fatigue in multiple sclerosis patients.

Fatigue is the most frequent symptom in multiple sclerosis (MS), although it is still poorly understood due to its complexity and subjective nature. There is an urgent need to identify reliable biomarkers to improve disease prognosis and therapeutic strategies. Epstein-Barr virus (EBV) is the major environmental risk factor associated with MS aetiology, and trials with EBV-targeted T cell therapies have reduced fatigue severity in MS patients. We investigated whether the serum amount of immunoglobulin (Ig)G-specific for EBV antigens could be a suitable prognostic marker for the assessment of MS-related fatigue. A total of 194 MS patients were enrolled. We quantified EBV nuclear antigen 1 (EBNA1) and EBV viral capsid antigen (VCA) immunoglobulin (Ig) G levels and B cell-activating factor of the tumour necrosis factor family (BAFF) concentration in the serum of patients with relapsing-remitting MS (RRMS) and chronic progressive MS (CPMS), and we analysed their correlation with aspects of fatigue and other clinical disease parameters. A complete EBV seropositivity could be detected in our cohort. After adjusting for confounding variables and covariates, neither EBNA1 nor VCA antibody titres were associated with levels of fatigue, sleepiness, depression, or with any of the clinical values such as expanded disability status scale, lesion count, annual relapse rate, or disease duration. However, patients with RRMS had significantly higher EBNA1 IgG titre than those with CPMS, whereas this was not the case under therapies targeting CD20+ cells. BAFF levels in serum were inversely proportional to anti-EBNA1 IgG. Our results show that EBNA1 IgG titre is not associated with the presence or level of fatigue. Whether the increased EBNA1 titre in RRMS plays a direct role in disease progression, or is only a consequence of excessive B cell activation, remains to be answered in future studies.

Frequent intrathecal production of antibodies to the viral capsid antigen of Epstein-Barr virus in patients with central nervous system post-transplant lymphoproliferative disorder

Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is strongly associated with Epstein-Barr virus (EBV). We analysed intrathecal production of EBV viral capsid antigen (VCA) immunoglobulin (Ig)G and IgA and Epstein-Barr nuclear antigen-1 (EBNA-1) IgG in nine patients with PNCS-PTLD and 20 patients with non-inflammatory neurological diseases (NINDs). Intrathecally produced VCA-IgG was detected in 7/9 (78%), VCA-IgA in 6/9 (67%) and EBNA-1-IgG in 2/9 (22%) patients with PCNS-PTLD, but not in NINDs. This exploratory study suggests that intrathecal EBV antibody production might be frequent in PCNS-PTLD. Detecting intrathecally produced VCA-IgG and VCA-IgA could thus potentially be helpful for diagnosing PCNS-PTLD.

Analytical performance evaluation of the Elecsys Epstein-Barr virus immunoassay panel

We evaluated the analytical performance of the Elecsys® Epstein-Barr virus (EBV) immunoassay panel for the in vitro detection of EBV immunoglobulin M (IgM), EBV viral capsid antigen immunoglobulin G (VCA IgG), and EBV nuclear antigen immunoglobulin G (EBNA IgG). Relative sensitivity/specificity were assessed using 1,734 human blood samples (1,068 residual samples from routine EBV testing; 467 presumed acute infection; 199 presumed seronegative) tested with the Elecsys EBV and 2 comparator panels (ARCHITECT EBV; Liaison EBV). EBV infection status was defined by majority approach. The three panels demonstrated comparable relative sensitivities/specificities, ranging between values (%) of 98.3−99.5 / 96.9−97.4 (EBV IgM); 96.3−98.4 / 98.4−98.7 (EBV VCA IgG); and 98.1−99.5 / 99.1−99.5 (EBV EBNA IgG). The Elecsys EBV IgM assay demonstrated superior analytical specificity in samples containing potential interferents. Utilizing the Elecsys EBV panel for the EBNA-first approach showed 97.5% overall agreement versus the majority approach in samples with clear EBV status.

Seroepidemiological Study of Epstein-Barr Virus in Patients with Head and Neck Tumors at Shahid Rajaee Hospital in Babolsar, Iran

Background: Epstein-Barr virus (EBV) is a herpes virus, which is the cause of infectious mononucleosis. Seroepidemiological studies show that more than 95% of adults in the world are infected with this virus. This virus is a modifying virus that is associated with some malignancies such as Burkitt lymphoma, tumors in HIV-infected patients, Hodgkin's lymphoma, head and neck tumors, and T-cell lymphoma. Objectives: This study aimed to determine the prevalence of EBV and its relation to the type of cancer in patients with head and neck tumors, which were treated in the years 2015 to 2016 at Shahid Rajaee Radiation Hospital in Babolsar. Methods: During one year, all patients with head and neck tumors were monitored, and finally, a total of 37 patients who had pathologically confirmed diagnoses were entered into the study after obtaining written informed consent. In this descriptive study, specific anti-EBV viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA). Also, other patients' information was obtained from their records. Results: The mean age of the patients was 59 years, and the number of men (70.23%) was higher than that of women (29.77%). Regarding the histopathology information and the frequency of tumors, most of the patients had squamous cell carcinoma (SCC) (73%) in the sites of the nasopharynx (27.02%) and pharynx (18.91%). The results of the ELISA test showed that IgG antibodies were positive in most of the patients (86.5 %). About the relation between the sites of the tumors and the IgG antibody, all patients (100%) with nasopharyngeal, tongue, and lips cancers were positive while they were the least in pharyngeal cancer (5.4%). Conclusions: This study showed that a significant number of patients with head and neck tumors (86.5%) were infected with this virus, which indicates that EBV as a carcinogenic agent in head and neck tumors has a high prevalence in our society and requires preventive and therapeutic actions.

Wild-type IDH2 contributes to Epstein–Barr virus-dependent metabolic alterations and tumorigenesis

ObjectiveEpstein–Barr virus (EBV) is a well-recognized oncogenic virus that can induce host cell metabolic reprogramming and tumorigenesis by targeting vital metabolic enzymes or regulators. This study aims to explore the role of wild-type isocitrate dehydrogenase 2 (IDH2) in metabolic reprogramming and tumorigenesis induced by EBV-encoded latent membrane protein 1 (LMP1). MethodsMechanistic dissection of wild-type IDH2 in EBV-LMP1-induced tumorigenesis was investigated using western blotting, real-time polymerase chain reaction (PCR), immunochemistry, chromatin immunoprecipitation (ChIP), and luciferase assay. The role of wild-type IDH2 was examined by cell viability assays/Sytox Green staining in vitro and xenograft assays in vivo. ResultsIDH2 over-expression is a prognostic indicator of poorer disease-free survival for patients with head and neck squamous cell carcinoma (HNSCC). IDH2 expression is also upregulated in nasopharyngeal carcinoma (NPC, a subtype of HNSCC) tissues, which is positively correlated with EBV-LMP1 expression. EBV-LMP1 contributes to NPC cell viability and xenograft tumor growth mediated through wild-type IDH2. IDH2-dependent changes in intracellular α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG) contribute to EBV-LMP1-induced tumorigenesis in vitro and in vivo. Elevated serum 2-HG level is associated with high EBV DNA and viral capsid antigen-immunoglobulin A (VCA-IgA) levels in patients with NPC. A significantly positive correlation exists between serum 2-HG level and regional lymph node metastases of NPC. EBV-LMP1 enhances the binding of c-Myc with the IDH2 promoter and transcriptionally activates wild-type IDH2 through c-Myc. Targeting IDH2 decreased intracellular 2-HG levels and survival of EBV-LMP1-positive tumor cells in vitro and in vivo. ConclusionsOur results demonstrate that the EBV-LMP1/c-Myc/IDH2WT signaling axis is critical for EBV-dependent metabolic changes and tumorigenesis, which may provide new insights into EBV-related cancer diagnosis and therapy.

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences

BackgroundAdolescent females have a higher prevalence of depression in comparison to their male peers – a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. MethodsA representative community sample of 259 female and 279 male adolescents aged 11–17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. ResultsIn multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit=−1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. ConclusionsDepressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.

Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis.

ObjectiveTo investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS).MethodsEBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89).ResultsEBNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS.ConclusionsWhile these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease.

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

A new gold nanoparticle based rapid immunochromatographic assay for screening EBV-VCA specific IgA in nasopharyngeal carcinomas

Large screening programs of nasopharyngeal carcinoma (NPC) are still challenging due to the scarcity of the resources in higher prevalence parts of the world. In the present study, the development of a new low cost immunochromatography (ICG) strip test for screening of nasopharyngeal carcinoma is reported. A conjugate of gold nanoparticle-anti viral capsid antigen (VCA) immunoglobulin A (IgA) antibody was used as the detection probe. The test is based on a non-competitive immunoassay for rapid and reliable detection the serum specific IgA of Epstein–Barr virus (EBV) VCA. Patient serum samples were analyzed with the strip and compared with enzyme-linked immunosorbent assay (ELISA) and pathological evaluation. The obtained results from the ICG strips were well correlated with the two reference methods. An evaluation of stability, sensitivity and specificity suggested the strip suitable for NPC screening programs in high-risk peoples and also for the recurrence monitoring.

Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7–52.6/89.4–97.8%] and 55.4/95.7% (95% CI, 45.7–64.7/90.4–98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771–0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810–0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6–87.0%) and a specificity of 90.6% (95% CI, 84.1–94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

A Case of Conjunctival Mass with Infectious Mononucleosis by EBV

Purpose: To report a case of conjunctival mass with infectious mononucleosis by Epstein-Barr virus (EBV) confirmed with Epstein-Barr encoding region (EBER) in situ hybridization. Case summary: A 8 year-old male without underlying disease was referred with counjunctival mass on the right eye starting 3 days ago. In ophthalmologic evaluation, there was injected, nontender, and “salmon patch” appearance conjunctival lesion on right superior bulbar conjunctiva. The patient was admitted to pediatrics with sore throat and fever. The tonsil were enlarged and white blood cell count was 14960/uL. EBV polymerase chain reaction (PCR) test and Viral capsid antigen Immunoglobulin M (VAC IgM) test were positive, the diagnose of infectious mononucleosis by EBV was made. After 5 days steroid eyedrop therapy, biopsy was performed because the lesion was not improved. There were lymphocyte infiltration, chronic inflammation and positive in EBER in situ hybridization. Conclusions: Elevated and pinkish lesion on conjunctiva, EBV lesion should be considered as differential diagnosis. J Korean Ophthalmol Soc 2014;55(10):1554-1557

Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

As diagnosis of nasopharyngeal carcinoma at an early disease stage is important, we attempted to distinguish between patients with nasopharyngeal carcinoma and noncancer controls by using serum protein profiles. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and CM10 protein chip were used to detect the serum proteomic patterns of 65 patients with nasopharyngeal carcinoma before radiotherapy and 93 noncancer controls. Proteomic spectra of serum samples from 50 nasopharyngeal carcinoma patients and 60 noncancer controls were used as a training set. The validity of the classification tree was then challenged with a blind test set which included another 15 patients with nasopharyngeal carcinoma and 33 noncancer controls. Biomarker Wizard 3.01 and Biomarker Pattern 5.01 were used in combination to analyze the data and to develop diagnostic models. 21 protein peaks were significantly different between nasopharyngeal carcinoma and controls. 4 mass peaks (M4182, M5343, M5913 and M8702 mass/charge ratio) were chosen automatically to construct a classification tree. The classification tree correctly determined 93.8% (45/48) of the test samples with 93.3% (14/15) of the nasopharyngeal carcinoma samples and 93.9% (31/33) of the noncancer samples. Using a combination of serum protein profiles and Epstein-Barr viral capsid antigen immunoglobulin A antibody tests, the diagnostic sensitivity and specificity were increased to 100 and 97%, respectively. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry could correctly distinguish nasopharyngeal carcinoma from noncancer individuals and showed great potential for the development of a screening test for the detection of nasopharyngeal carcinoma.

Early detection of nasopharyngeal carcinoma by plasma Epstein‐Barr virus DNA analysis in a surveillance program

Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

Joint Effects of Epstein-Barr Virus and Polymorphisms in Interleukin-10 and Interferon-γ on Breast Cancer Risk

The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-γ (IFN-γ) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-γ rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-γ rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-γ.

Maternal Depression and Epstein-Barr Virus Reactivation in Early Pregnancy

Recent evidence suggests a link between Epstein-Barr virus reactivation and chronic stress due to decreased cellular immune responses. Maternal depression complicates 10% to 20% of pregnancies and is accompanied by stress. We sought to estimate the association of Epstein-Barr virus reactivation with depression in pregnancy. In this cohort study, prevalence of Epstein-Barr virus reactivation was compared between 100 pregnant women with depression before pregnancy and a computer-generated referent group of 100 healthy women not known to be depressed. We included only those women with documented Diagnostic and Statistical Manual of Mental Disorders depression diagnoses in the current pregnancy. Serum samples were analyzed for presence of Epstein-Barr virus viral capsid antigen, nuclear antigen, and early antigen antibodies. Epstein-Barr virus reactivation was defined by presence of viral capsid antigen or nuclear antigen immunoglobulin (Ig) G, along with early antigen IgG, viral capsid antigen IgM, or both early antigen IgG and viral capsid antigen IgM. Maternal demographics were similar between the groups except for older age (34.1 compared with 32.7 years, P=.05), and lower body mass index (27.3 compared with 28.9, P=.03) among the depressed individuals. Ninety-five percent of the women were seropositive for Epstein-Barr virus. Women with depression were more likely to have Epstein-Barr virus reactivation (48% compared with 30%, P=.01) when compared with referent participants. Epstein-Barr virus reactivation remained associated with maternal depression (adjusted odds ratio 1.97, 95% confidence interval 1.10-3.77, P=.03) after controlling for potential confounders. Women with depression have higher prevalence of Epstein-Barr virus reactivation, possibly due to increased stress. II.

Clinical features of Epstein-Barr virus-associated infectious mononucleosis in hospitalized Korean children

PurposeFew studies have been conducted on the recent status of infectious mononucleosis (IM) in Korean children. The aim of this study was to evaluate the recent trend in the clinical manifestations of Epstein-Barr virus (EBV)-associated IM as well as the clinical differences according to age.MethodsA retrospective study was performed on 81 children hospitalized with EBV-associated IM who fulfilled the serological criteria for the diagnosis of EBV infection (viral capsid antigen immunoglobulin M positive). The patients were divided into 3 age groups: <5 years, 5 to 9 years, and ≥10 years. We evaluated the recent trend in clinical manifestations and the differences in clinical and laboratory findings among the 3 age groups.ResultsThirty (37%) children were under 5 years of age, 38 (46.9%) were 5 to 9 years of age, and 13 (16%) were 10 years of age or older. The differences in the symptoms and signs among the 3 age groups were not statistically significant, except for headache. The mean duration of fever was 7.7 days (range, 0 to 18 days). A comparison of liver enzyme elevation among the age groups showed an association with advancing age (26.6%, 63.1%, and 76.9%, respectively, P=0.04)ConclusionThis study showed that EBV-associated IM in Korean children continues to occur mostly in children under 10 years of age. In children with EBV-associated IM, the incidence of headache and liver enzyme elevation, the duration of fever, and the proportion of females to males were all positively associated with advancing age.

Familial Tendency and Risk of Nasopharyngeal Carcinoma in Taiwan: Effects of Covariates on Risk

In the present study, the authors compared the long-term risk of nasopharyngeal carcinoma (NPC) of male participants in an NPC multiplex family cohort with that of controls in a community cohort in Taiwan after adjustment for anti-Epstein-Barr virus (EBV) seromarkers and cigarette smoking. A total of 43 incident NPC cases were identified from the 1,019 males in the NPC multiplex family cohort and the 9,622 males in the community cohort, for a total of 8,061 person-years and 185,587 person-years, respectively. The adjusted hazard ratio was 6.8 (95% confidence interval (CI): 2.3, 20.1) for the multiplex family cohort compared with the community cohort. In the evaluation of anti-EBV viral capsid antigen immunoglobulin A and anti-EBV deoxyribonuclease, the adjusted hazard ratios were 2.8 (95% CI: 1.3, 6.0) and 15.1 (95% CI: 4.2, 54.1) for those positive for 1 EBV seromarker and positive for both seromarkers, respectively, compared with those negative for both EBV seromarkers. The adjusted hazard ratio was 31.0 (95% CI: 9.7, 98.7) for participants who reported a family history of NPC and who were anti-EBV-seropositive compared with individuals without such a history who were anti-EBV-seronegative. The findings suggest that both family history of NPC and anti-EBV seropositivity are important determinants of subsequent NPC risk and that the effect of family history on NPC risk cannot be fully explained by mediation through EBV serologic responses.