Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients.

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3⁺ cells, helper CD4⁺ cells and CD19⁺ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3⁺ and CD4⁺ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

Relative EBV antibody concentrations and cost of standard IVIG and CMV-IVIG for PTLD prophylaxis in solid organ transplant patients.

Some centers prefer CMV-IVIG over IVIG for the prophylaxis of EBV-related PTLD in solid organ transplant patients. Our objective was to compare the relative dose-related EBV ELISA antibody concentrations and cost of standard IVIG and CMV-IVIG. The concentration of EBV IgG to VCA was analyzed via ELISA in four lots of IVIG and four lots of CMV-IVIG. Relative EBV ELISA antibody concentrations and cost were compared assuming an IVIG dose of 0.5 gm/kg and CMV-IVIG dose of 0.15 gm/kg in a 50-kg patient. The price of IVIG was $70/gm and CMV-IVIG $430/gm. IVIG contains the same EBV antibody concentrations (20 790 ELISA antibody units/mL) than CMV-IVIG (17 430 ELISA antibody units/mL, p > 0.2) in the four lots of each product sampled. When factoring in the dosing scheme for a 50-kg patient, IVIG contains two times more EBV antibody than CMV-IVIG. Yet, CMV-IVIG is 1.8 times more expensive than IVIG ($3225 vs. $1750). In the four lots of each product sampled, IVIG contains more EBV antibodies and costs less than CMV-IVIG when factoring in the dosing scheme. Studies are needed to determine whether there is clinical efficacy of immunoglobulin products for EBV-related PTLD prophylaxis.

OPTN/SRTR 2012 Annual Data Report: liver.

Liver transplant in the us remains a successful life-saving procedure for patients with irreversible liver disease. In 2012, 6256 adult liver transplants were performed, and more than 65,000 people were living with a transplanted liver. The number of adults who registered on the liver transplant waiting list decreased for the first time since 2002; 10,143 candidates were added, compared with 10,359 in 2011. However, the median waiting time for active wait-listed adult candidates increased, as did the number of candidates removed from the list because they were too sick to undergo transplant. The overall deceased donor transplant rate decreased to 42.3 per 100 patient-years, and varied geographically from 18.9 to 228.0 per 100 patient-years. Graft survival continues to improve, especially for donation after circulatory death livers. The number of new active pediatric candidates added to the waiting list also decreased. Almost 75% of pediatric candidates listed in 2009 underwent transplant within 3 years; the 2012 rate of deceased donor transplants among active pediatric wait-listed candidates was 136 per 100 patient-years. Graft survival for deceased donor pediatric transplants was 92.8% at 30 days. Medicare paid for some or all of the care for more than 30% of liver transplants in 2010.

OPTN/SRTR 2012 Annual Data Report: pancreas.

The number of pancreas transplants has decreased over the past decade, most notably numbers of pancreas after kidney (pak) and pancreas transplant alone (pta) procedures. This decrease may be mitigated in the future when changes to national pancreas allocation policy approved by the Organ Procurement and Transplantation Network Board of Directors in 2010 are implemented. The new policy will combine waiting lists for pak, pta, and simultaneous pancreas-kidney (spk) transplants), and give equal priority to candidates for all three procedures. This policy change may also eliminate geographic variation in waiting times caused by geographic differences in allocation policy. Deceased donor pancreas donation rates have been declining since 2005, and the donation rate remains low. The outcomes of pancreas grafts are difficult to describe due to lack of a uniform definition of graft failure in the transplant community. However long-term survival is better for spk versus pak and pta transplants. This may represent the difficulty of detecting rejection in the absence of a simultaneously transplanted kidney. The challenges of pancreas transplant are reflected in high rates of rehospitalization, most occurring within the first 6 months posttransplant. Pancreas transplant is associated with higher incidence of rejection compared with kidney transplant.

Epstein-Barr virus antibody titer and its association with the domain scores from the World Health Organization's Quality of Life questionnaire: Findings from Rural Hainan Province, China.

OBJECTIVE: Epstein-Barr virus (EBV) antibody titer has recently been used as a biomarker of psychological stress. This is the first study to investigate the association between EBV antibody titer and perceived quality of life (QOL) in Hainan Island, China. METHODS: Participants from two regions of Hainan Island, recruited into a larger study investigating the health impact of rapid economic development among rural residents, were stratified by age, sex, and region; 15 people were randomly selected from each of the 16 subgroups, to give a total sample size of 240. EBV antibody titer in dried blood spot samples was measured by enzyme-linked immunosorbent assay. The abbreviated version of the World Health Organization's Quality of Life questionnaire was used to gather information on six categories of QOL. Multiple linear regression analysis was used to examine the relationship between EBV antibody titer and QOL. RESULTS: After adjusting for the effects of age, sex, region and C-reactive protein concentration, EBV antibody titer was negatively associated with the physical (P = 0.044) and psychological QOL domains (P = 0.039). CONCLUSION: This study suggests that among individuals living in an environment in the initial stages of economic development EBV antibody titer, a biomarker of psychological stress, is not only associated with the psychological aspects of QOL but is also linked to physical problems.

Seroepidemiology of Epstein-Barr virus and cytomegalovirus among Israeli male young adults.

PURPOSE: To assess the seroprevalence and seroconversion of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Immunoglobulin G (IgG) antibodies and identify associated socioeconomic and smoking variables among male young adults in Israel, to explore health disparities and aid prevention efforts. METHODS: A population-based seroprevalence study of EBV and CMV IgG antibodies in a systematic sample of Israeli males upon recruitment to mandatory military service during 1994-2004. Associations between socioeconomic and smoking variables and the seroprevalence of EBV/CMV were evaluated, controlling for possible confounders. A subset of seronegative subjects was assessed for seroconversion upon discharge from military service. RESULTS: Overall seroprevalence rates were 87% for EBV and 59% for CMV. An association between the seroprevalence of EBV and CMV was observed. Seroconversion was 56% for EBV as compared with 31% for CMV. Lower paternal education was found to be associated with both EBV and CMV seroprevalence. Lower socioeconomic status, North African origin, and urban residence were found to be associated with CMV seropositivity, as was smoking for EBV seropositivity. CONCLUSIONS: Socioeconomic disparities exist in the seroprevalence rates of CMV and EBV among Israeli male young adults. The results of the study could aid public health efforts and determine target populations when a vaccine becomes available.

Comparison of a multiplexed bead-based assay with an immunofluorescence and an enzyme-immuno assay for the assessment of Epstein-Barr virus serologic status.

We have compared a multiplexed bead-based assay (BBA) with an enzyme immunoassay (EIA) and immunofluorescence assay (IFA) for the assessment of the Epstein-Barr virus (EBV) serostatus. Three hundred and ninety-three sera, classified according to IFA results as seronegative (n=100), acute infection (n=100), past infection (n=100) and indeterminate (n=93), were tested by BBA and EIA. Overall, the three methods gave similar results with a relatively high (75.2%) concordance with the consensus interpretation of the serostatus. The most significant discordances were: (i) 58 samples had uninterpretable results for BBA, in majority due to the detection of non-antigen specific antibody binding by control beads. (ii) almost half the samples positive for anti-Epstein-Barr nuclear antigen (EBNA) IgG by BBA or EIA were negative by IFA. Among the latter, only a minority had a history of immunocompromise or treatment, or detectable anti-early antigen antibody. This discrepancy probably reflects a poor sensitivity of IFA for anti-EBNA IgG detection. EIA and BBA had a similar performance and had substantial practical advantages over IFA with respect to testing for EBV serostatus.

Evaluation of Epstein-Barr virus antibodies, anti-VCA avidity by immunofluorescence and immunoblot assays for assessment of Epstein-Barr virus immunologic state.

Three hundred twenty two serum samples were evaluated by indirect immunofluorescence assay (IFA) and immunoblotting for the assessment of the immunologic status of Epstein-Barr virus (EBV). Serological profiles of 322 serum samples were classified by the IgM and IgG antibodies by the immunofluorescence assay as seronegative, acute infection, reactivation and past infection. Higher rates of seropositivity were determined in serum samples belonging to old age groups. Routine tests used for EBV diagnosis were efficient.

Lifestyle incongruity, stress and immune function in indigenous Siberians: the health impacts of rapid social and economic change.

The purpose of this study was to investigate the impact of economic and cultural change on immune function and psychosocial stress in an indigenous Siberian population. We examined Epstein-Barr virus antibodies (EBV), an indirect biomarker of cell-mediated immune function, in venous whole blood samples collected from 143 Yakut (Sakha) herders (45 men and 98 women) in six communities using a cross-sectional study design. We modeled economic change through the analysis of lifestyle incongruity (LI), calculated as the disparity between socioeconomic status and material lifestyle, computed with two orthogonal scales: market and subsistence lifestyle. EBV antibody level was significantly negatively associated with both a market and a subsistence lifestyle, indicating higher cell-mediated immune function associated with higher material lifestyle scores. In contrast, LI was significantly positively associated with EBV antibodies indicating lower immune function, and suggesting higher psychosocial stress, among individuals with economic status in excess of material lifestyle. Individuals with lower incongruity scores (i.e., economic status at parity with material resources, or with material resources in excess of economic status) had significantly lower EBV antibodies. The findings suggest significant health impacts of changes in material well-being and shifting status and prestige markers on health during the transition to a market economy in Siberia. The findings also suggest that relative, as opposed to absolute, level of economic status or material wealth is more strongly related to stress in the Siberian context.

Social stressors, mental health, and physiological stress in an urban elite of young Afghans in Kabul.

Afghanistan provides a unique setting in which to appraise psychosocial stress, given the context of persistent insecurity and widening economic inequality. In Kabul, people experience widespread frustrations, hinging on restricted opportunities for social advancement, education, and employment. We appraised social aspirations, every-day stressors, psychosocial distress, and mental health problems for a random sample of 161 male and female students at Kabul University. The survey featured both existing and newly-developed instruments (Self-Reported Questionnaire SRQ-20; Afghan Symptom Checklist; Afghan Daily Stressor Scale; and Social Aspirations and Frustrations), implementing both internationally-used and culturally-grounded measures of mental health assessment. We also included indicators of physical health (blood pressure, immune responses to Epstein-Barr virus (EBV), C-reactive protein, and body mass index), to map physiological function with reported psychosocial distress. This young, urban elite expressed major feelings of frustrations, related to physical, economic, social, and political stressors of day-to-day life in Kabul. There were striking gender differences for psychosocial and physiological markers of wellbeing; specifically, women showed poorer mental health (SRQ-20, P = 0.01) and elevated EBV antibody titers (P = 0.003). Both diastolic blood pressure (P = 0.018) and EBV (P = 0.038) were associated with a subscale of family stressors among women, but not among men, consistent with women's social vulnerabilities to stressful family dynamics. This is the first study to integrate approaches from anthropology, cross-cultural psychiatry, and human biology to document social stressors, psychosocial distress, and physiological wellbeing in the challenging setting of present-day Afghanistan.

Evaluation of a multiplexed bead assay for assessment of Epstein-Barr virus immunologic status.

Currently, serological assays using either indirect immunofluorescence assay or enzyme-linked immunosorbent assay (ELISA) are performed to evaluate the status of Epstein-Barr virus (EBV) infection in humans. Although these methods are reliable, they are limited to testing an antibody response to a single viral antigen per reaction, thus necessitating a panel of assays to complete the evaluation. In contrast, a new bead-based method (BioPlex 2200; Bio-Rad Laboratories, Hercules, Calif.) can analyze the humoral response to multiple antigens in a single tube. This approach potentially reduces overall cost, turnaround time, and sample volume. The aim of this study was to evaluate the multiplexed EBV serologic assays performed on the BioPlex 2200 platform compared to results of conventional heterophile and ELISA-based assays. A total of 167 nonconsecutive, stored serum samples from adult and pediatric patients submitted for EBV serologic studies were used in the evaluation. Concordance between results generated by the BioPlex 2200 system and conventional assays was calculated. The anti-EA-D assay had the lowest concordance at 91%. The BioPlex 2200 system showed 97% agreement with conventional heterophile and anti-nuclear antigen assays and 92% agreement with the anti-VCA IgG and immunoglobulin M assays. Agreement between the BioPlex 2200 system and conventional testing was 92% with respect to categorization of acute versus nonacute EBV disease. The correlation between these two systems with regard to assignment into one of four categories of EBV status was also good (82%). In summary, there is excellent correlation between contemporary EBV serologic testing and the BioPlex 2200 system.

Assessment of Epstein-Barr virus association with pediatric non-hodgkin lymphoma in immunocompetent and in immunocompromised patients in Argentina.

CONTEXT: Epstein-Barr virus (EBV) has been classically associated with 3 malignancies, Burkitt lymphoma, B-cell lymphoproliferative syndromes, and nasopharyngeal carcinoma, and more recently with Hodgkin disease, T-cell lymphomas, and gastric and breast carcinomas, as well as with leiomyosarcoma and leiomyoma associated with immunosuppression. OBJECTIVE: To compare EBV expression in Argentine tumor samples with those reported elsewhere, we analyzed EBV expression in an Argentine pediatric population with non-Hodgkin lymphoma and correlated these results with clinical course and outcome. METHODS: We studied EBV presence by latent membrane protein-1 protein labeling by immunohistochemistry, by in situ hybridization, and by polymerase chain reaction for Epstein-Barr-encoded RNAs (EBERs) in formalin-fixed and paraffin-embedded non-Hodgkin lymphoma tissue samples (collected retrospectively) from 32 pediatric patients at Ricardo Gutiérrez Children's Hospital from 1993 to 2000. RESULTS: Eight out of the 32 (25%) non-Hodgkin lymphoma cases showed latent membrane protein-1 and EBERs by in situ hybridization positive staining in tumor cells. Among EBERs and latent membrane protein-1-positive cases, there were 5 immunocompromised patients, with either human immunodeficiency virus infection or primary immunodeficiency. The EBERs in situ hybridization results were confirmed by EBERs polymerase chain reaction in good-quality DNA from 11 samples, with 3 proving positive and 8 negative. CONCLUSIONS: The association of EBV with non-Hodgkin lymphoma in the Argentine pediatric population was low (25%), and this figure rose to 100% when only the immunocompromised patients subgroup was considered, confirming that the virus is probably a cofactor in the lymphomagenesis of some but not all pediatric non-Hodgkin lymphoma. So far, no differences in clinical outcome are discernible between EBV-positive and EBV-negative non-Hodgkin lymphoma patients.

Assessment of the relationship of chronic opisthorchiasis to Epstein-Barr virus infection as well as some cytogenetical and immunological parameters in two comparable Siberian regions.

Previous studies have shown an increase in the frequency of chromosomal abnormalities in the peripheral blood lymphocytes from opisthorchiasis patients. Some evidence suggests that there is an association between chronic opisthorchiasis and certain herpes viruses. To study the relationship of opisthorchiasis to the reactivation of Epstein-Barr virus (EBV) infection as well as the influence of opisthorchis infection on some cytogenetical and immunological parameters, we used the indirect immunofluorescence for measuring some virus specific antibodies, the cytokinesis-block lymphocyte micronucleus assay, and the quantitative immunodiffusion method for measuring immunoglobulin concentrations in serum. A total of 1,580 people were monitored in two comparable Siberian regions: in the Ob River region which is endemically related to opisthorchiasis caused by Opisthorchisfelineus and in the nonendemic control Yenisey River region. There was no significant difference in each of the tested parameters between two uninfected controls from the endemic Ob and nonendemic Yenisey regions. We have found significant difference (p < 0.01) in the frequency of micronucleated cytokinesis-block lymphocytes and the antibody levels against certain EBV antigens between the examined inhabitants of the opisthorchis-infected Ob and uninfected Yenisey regions. Furthermore, there were a good correlation (r = + 0.72) between the increase in titres of antibody to the EBV capsid antigen and the high frequency of micronucleated lymphocytes in the opisthorchis-infected Ob population. Also, levels of both IgG and IgM were increased in opisthorchiasis patients. This study confirms an association between chronic opisthrochiasis and reactivation of EBV which may be implicated in the development of cancer in opisthorchiasis patients.

A new method with general diagnostic utility for the calculation of immunoglobulin G avidity.

The reference method for immunoglobulin G (IgG) avidity determination includes reagent-consuming serum titration. Aiming at better IgG avidity diagnostics, we applied a logistic model for the reproduction of antibody titration curves. This method was tested with well-characterized serum panels for cytomegalovirus, Epstein-Barr virus, rubella virus, parvovirus B19, and Toxoplasma gondii. This approach for IgG avidity calculation is generally applicable and attains the diagnostic performance of the reference method while being less laborious and twice as cost-effective.