Viral Capsid Antigen Antibody Research Articles

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.

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (β = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Expression of Serum Sialic Acid, Early Antigen-IgA, and Viral Capsid Antigen-IgA in Nasopharynx Cancer Patients: The Diagnostic Implication of Combined Assays.

BackgroundEbstein-Barr virus (EBV) plays a critical role in nasopharynx cancer, which can be effectively monitored by serum levels of early antigen antibody (EA-IgA) and viral capsid antigen antibody (VCA-IgA). This study explored the diagnostic value of combined assays of sialic acid (SA), EA-IgA, and VCA-IgA via the expressional assay.Material/MethodsA total of 42 nasopharynx cancer patients and 42 benign rhinitis and healthy controls were recruited in this study. Serum EA-IgA and VCA-IgA were tested by enzyme-linked immunosorbent assay (ELISA) and enzymatic assay of serum SA. Specificity and sensitivity of those 3 assays were compared. The diagnostic value of each parameter was evaluated by ROC curves.ResultsAll 3 indexes (SA, EA-IgA and VCA-IgA) showed elevated serum levels in nasopharynx cancer patients when compared to those with rhinitis, who had higher levels than healthy individuals. Concentrations of these factors were also positively correlated with the TNM staging of cancer. The sensitivity and specificity were 30.95% and 83.33% (in SA), 57.14% and 95.24% (in EA-IgA), and 76.19% and 92.86% (in VCA-IgA), respectively. VCA-IgA had the highest sensitivity among all 3 indexes. The combined assay increased the diagnostic sensitivity to 92.86% without compromising specificity.ConclusionsSA, EA-IgA, and VCA-IgA levels were significantly elevated in nasopharynx patients’ serum. The combined assay may have clinical value in diagnosis and monitoring.

Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: Results from the Multi-Center SET study

ObjectivesTo investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. MethodsWe analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein–Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24months. ResultsAnti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. ConclusionsAntibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

Epstein–Barr Virus Infection Induces Aberrant TLR Activation Pathway and Fibroblast–Myofibroblast Conversion in Scleroderma

Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein–Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV–Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation.

Interactions of serum cholesterol with anti-herpesvirus responses affect disease progression in clinically isolated syndromes

ObjectivesTo investigate whether anti-herpesvirus antibodies are associated with serum cholesterol profiles in clinically isolated syndromes (CIS). MethodsPre-treatment serum samples from 118 high-risk CIS patients were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1). A lipid profile consisting of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) was obtained. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24months after start of interferon-beta treatment. ResultsThe study included 118 CIS patients (77 females, 41 males, 65.3% female; mean age: 28.1±SD 8.1years). Anti-EBV EBNA-1 antibody levels were associated with LDL-C (p=0.009) and TC (p=0.008) levels. Anti-CMV positivity status was associated with reduced time to relapse (p=0.006) and the greater number of relapses (p=0.009) in patients with high HDL-C. Anti-EBV VCA antibody levels were associated with greater number of new T2 lesions (p=0.002) and with increased brain atrophy (p<0.001) in patients with high LDL-C. ConclusionsOur results indicate that higher levels of anti-EBV EBNA-1 antibodies are associated with higher LDL-C and TC levels. Anti-CMV positive individuals have greater disease progression in the presence of higher HDL-C levels. Individuals with higher levels of anti-EBV VCA antibodies have greater progression on MRI measures in the presence of higher LDL-C.

Social support and socioeconomic status interact to predict Epstein-Barr virus latency in women awaiting diagnosis or newly diagnosed with breast cancer.

Both higher socioeconomic status (SES) and supportive personal relationships confer health benefits, including better immune function. This study assessed the joint impact of SES and social support on the expression of a latent herpesvirus, Epstein-Barr virus (EBV), in a group of highly stressed women. Two-hundred and twenty four women either awaiting further evaluation following an abnormal mammogram or newly diagnosed with breast cancer completed questionnaires and provided blood samples to assess EBV viral capsid antigen (VCA) IgG antibody titers. More highly educated women with more support from friends had lower EBV VCA antibody titers, reflecting a stronger cellular immune response to the latent virus; however, among less educated women, friend support was not associated with EBV antibody titers. As revealed in an ancillary analysis, more highly educated women with more friend support had lower systolic blood pressure (SBP); however, friend support was not associated with SBP among less educated women. Neither depression nor perceived stress mediated these associations. Neither cancer status nor cancer stage among those diagnosed with cancer was significantly related to these outcomes. Lower SES women may not reap the same immunological benefits from friend support when experiencing a stressful life event as their higher SES counterparts.

Strong Correlations of Anti–Viral Capsid Antigen Antibody Levels in First‐Degree Relatives from Families with Epstein‐Barr Virus–Related Lymphomas

Markers of Epstein-Barr virus (EBV) infection include anti-viral capsid antigen (VCA) immunoglobulin (Ig) G. High anti-VCA titers are associated with EBV-related lymphoproliferation, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). Intrafamilial correlations of anti-VCA IgG levels were studied in 3 settings: 127 families recruited through patients with HL in France (population A), 31 families recruited through patients with BL in Uganda (population B), and 74 large families from a general population in Cameroon (population C). Titers were determined by enzyme-linked immunosorbent assay (populations A and C) or by immunofluorescence analysis (population B). In populations A and B, the anti-VCA IgG titers of the relatives of patients with HL or BL increased significantly (P = .01 and P < .001, respectively) with those of the index case patient. In all 3 populations, anti-VCA IgG titers were significantly correlated (P < .001 for A, P = .002 for B, and P < .001 for C) between genetically related individuals (father-offspring, mother-offspring, and sibling-sibling) but not between spouses. Similar results were obtained for population A after adjustment for total IgG levels. In all cases, the pattern of correlations was consistent with a polygenic model, with heritability ranging from 0.32 to 0.48. These results provide evidence for the genetic control of anti-VCA IgG titers and pave the way for identification of the loci involved.

Comparison of immunofluorescence assay and multiplexed microparticle-based immunoassay for detecting Epstein-Barr virus viral capsid antigen antibodies

A new multiplexed microparticle-based immunoassay was compared with the immunofluorescence assay that is used widely for detecting EBV-specific antibodies in immunocompetent patients. Serum samples of 162 patients submitted for routine EBV diagnosis were tested for viral capsid antigen IgM, viral capsid antigen IgG and serological profile interpretations with both systems. The result concordances were 94.2%, 93.6%, and 92.1%, respectively. Multiplexed microparticle-based immunoassay can be an alternative to immunofluorescence assay especially in laboratories receiving large numbers of samples.

Correlations between Epstein-Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals

Background Female gender, human leukocyte antigen (HLA) DR2, tobacco smoking and Epstein-Barr virus (EBV) are established risk factors for multiple sclerosis (MS). Their possible interaction however, has been sparsely studied. Objectives To investigate possible associations between EBV antibody levels and a range of other recognized MS risk factors. Design, setting and study population Cross-sectional study undertaken in Denmark based on 517 healthy individuals selected from the Danish population. Methods We measured change in mean log (anti-Epstein-Barr viral capsid antigen (VCA) immune globulin G) using linear regression. Results Anti-Epstein-Barr VCA immune globulin G levels were positively correlated with female gender and HLA DR2. Furthermore, current smoking and cumulative tobacco consumption were positively associated with EBV antibody levels. Conclusion The association between Epstein-Barr VCA antibody levels and non-viral MS risk factors support the view that EBV is critically involved in the etiology of MS. These non-viral MS risk factors may be linked with MS risk through EBV-specific immune responses. Multiple Sclerosis 2007; 13: 420-423. http://msj.sagepub.com

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

Studies of anti-cytomegalovirus IgG antibody positive rate and cytomegalovirus mononucleosis in adults

We analyzed anti-Cytomegalovirus (CMV) IgG and IgM antibody (EIA) and anti-Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgG and IgM antibody (FA) in adults during 1994-1999. We examined these IgM sero-positive patient's medical records, and diagnosed CMV mononucleosis and EBV mononucleosis. Anti-CMV antibody positive rates decreased from 87.6% in 1994 to 77.8% in 1999. Especially in twenties, anti-CMV antibody positive rates decreased from 65.2% in 1994 to 53.3% in 1999. On the other hand, anti-EBV VCA antibody positive rates were not changed (91-94%). Number of cases of CMV mononucleosis increased from 2 cases in 1994 to 16 cases in 1999, but EBV mononucleosis was not changed. These results suggested that increasing cases of CMV mononucleosis was influenced by decreasing anti-CMV antibody positive rate.

Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students.

Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students.

Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students.

The relationship of individual differences in repressive coping styles with differences in antibody titer to Epstein-Barr viral capsid antigen (EBV-VCA) were investigated in a normal, healthy college population made up of people previously exposed to EBV. Each of 54 1st-year undergraduates completed a battery of physical-status questions and items pertaining to potential behavioral immunomodulatory confounds, along with the Taylor Manifest Anxiety Scale (T-MAS) and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Ss reporting high and middle levels of anxiety had higher antibody titers to EBV, suggesting poorer immune control over the latent virus, as compared with the low-anxious group. Similarly, high-defensive Ss had higher antibody titers than their low-defensive counterparts, and neither group differed from the middle group.

Assessment of serologic markers for Epstein-Barr virus.

Antibody responses to early antigen (EA) and viral capsid antigen (VCA) were analyzed in 48 proven cases of Epstein-Barr Virus infection and in 48 age- and sex-matched healthy controls to establish optimal cutoff values for diagnosing EBV infection. Predictive values were determined for individual EA and VCA antibody titers and for EA to VCA antibody ratios and the optimal dilution cutoff values for positivity of EA (1:20), VCA (1:640), and EA to VCA (0:031) were selected. When evaluated on a subset of 10 VCA IgM positive cases and 35 negative controls, the three selected cutoff values identified as infections nine of 10, four of 10, and 10 of 10 of the cases and one of 35, none of 35, and one of 35 of the controls, respectively. When evaluated individually on 22 cases of suspected EBV infection who were heterophile antibody-negative and presented with symptoms compatible with EBV infection, an equal number of VCA IgM-positive and negative cases were identified as EBV infections. Overall, the cutoffs EA, VCA, and ratio identified 19 of 22 (86.4%), 14 of 22 (63.6%), and 18 of 22 (81.8%), respectively, and all cases could be identified using combinations of these values. Although these serologic values may be used with some accuracy, until more definitive markers are described a combination of heterophile responses, lymphocyte analysis, clinical symptoms, and serologic cutoff values should be used to assess the role of EBV in patient evaluation.

Epstein-Barr virus-induced malignant lymphoma in a white-lipped marmoset.

One of six white-lipped marmosets inoculated with cell-free B95-8 virus developed diffuse malignant lymphoma. Epstein-Barr virus (EBV) DNA was detected in a pathologically enlarged mandibular lymph node by DNA-DNA hybridization. The affected animal at the time of killing had EBV antibody titers of 1:320 for viral capsid antigen (VCA) and 1:20 for early antigen (EA) while all non-diseased animals had less than or equal to 1:80 VCA antibody and no detectable EA antibody. This is the first report of lymphoma development in a white-lipped marmoset following EBV inoculation.

Enzyme immunoassay for detection of antibody to Epstein-Barr virus-specific early antigen

Antibody to Epstein-Barr virus-induced early antigen could be measured in sera using enzyme-linked antibody. The sensitivity of this assay was comparable to that of the indirect immunofluorescent technique. Measurement of early antigen was accomplished on a producer cell line which was specifically treated to block late gene expression. It is now possible to measure Epstein-Barr virus-induced early antigen and viral capsid antigen antibodies by using the same cell line.

Epstein-Barr virus-specific serum immunoglobulin A as an acute-phase antibody in infectious mononucleosis

Immunoglobulin A (IgA) antibodies to Epstein-Barr virus viral capsid antigen were assayed serially in 19 patients with infectious mononucleosis and in 38 controls. Seventy-four percent of infectious mononucleosis patients demonstrated IgA antibody, whereas this was found in 13% of controls. This antibody appeared early in infectious mononucleosis and was virtually gone 10 weeks after onset. Comparison of IgA antibody kinetics was made with IgG and IgM antibodies to viral capsid antigen, heterophile antibody, and antibody to Epstein-Barr virus early antigen and nuclear antigen. Failure to demonstrate IgA antibody was associated with severe illness, prolonged illness, delay in IgG and anti-Epstein-Barr virus nuclear antigen antibody, and low or absent heterophile and anti-early antigen antibody. Assay of IgA antibody to viral capsid antigen is a potentially useful adjunct in the serodiagnosis of infectious mononucleosis or recent Epstein-Barr virus infection, as are the other antibodies tested, but in this study IgM viral capsid antigen antibody was the only acute-phase antibody present in all patients.

Epstein-Barr Virus Antibodies in Sudanese Patients With Nasopharyngeal Carcinoma: A Preliminary Report&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;

With the use of an immunofluorescence technique Epstein-Barr viral capsid antigen antibody titers were determined in the sera from 226 Sudanese: 41 with nasopharyngeal carcinoma (NPC), 77 with other head and neck cancers, 21 with malignant lymphomas, 63 with other cancers, 6 with specific granulomas, and 18 normal controls. Of the NPC patients, 87.8% had titers of 320 or greater and 43.9% had titers of 2,560 or more, whereas none had titers of less than 40. Their geometric mean titer (GMT) level was 1,855. However, compared to the NPC patients, the other patients and normal controls showed significantly higher percentages of sera with low titers and lower percentages of sera with high titers and they had a GMT that was 4--16 times lower. The high NPC titers were independent of age, sex, tribe, or locality of patients. The preliminary results indicated the importance of future immunovirologic and immunogenetic field investigations on the natural history of the Epstein-Barr virus and on the genetics of the host.

Epstein-Barr Virus Infections in Brazil. II. Hodgkin's Disease2

Sixty-seven cases of Hodgkin's disease (HD) occurring in São Paulo, Brazil, were studied. Males with HD predominated over females 2.3 to 1. Sixty-six percent of the cases occurred in patients under 30 years of age, 31.7% under 20 years of age, and only 7.5% after 50 years of age. Lymphocyte predominance and mixed cellularity histologic types were most common in patients less than 15 years old, and nodular sclerosis was most common in the 15- to 19-year-old group. Sera from all patients had antibody to the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). The geometric mean titer (GMT) of VCA antibody with the use of Jijoye cells as antigen was 1:162, and 31.3% of patients had titers of 1:320 or more; in controls, the GMT was 1:67 and 3.8% had titers of 1:320 or more. Similar results were obtained when EB-3 cells were used as antigen. The highest titers occurred in males, in mixed cellularity and lymphocyte depletion forms, and in stage 2 of illness. EBV-specific IgM antibody and heterophile antibody levels were not elevated, but 20.5% of the HD patients had antibody to the early antigen of EBV present in their sera. Antibody levels for herpes simplex virus, cytomegalovirus, rubella, measles, parainfluenza viruses, and papovavirus were not significantly elevated over those in matched controls.