EBV VCA IgM Research Articles

Alzheimer's disease risk associated with changes in Epstein-Barr virus nuclear antigen 1-specific epitope targeting antibody levels

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder influenced by age, sex, genetic factors, immune alterations, and infections. Multiple lines of evidence suggest that changes in antibody response are linked to AD pathology. MethodsTo elucidate the mechanisms underlying AD development, we investigated antibodies that target autoimmune epitopes using high-resolution epitope microarrays. Our study compared two groups: individuals with AD (n = 19) and non-demented (ND) controls (n = 19). To validate the results, we measured antibody levels in plasma samples from AD patients (n = 96), mild cognitive impairment (MCI; n = 91), and ND controls (n = 97). To further explore the invlovement of EBV, we performed epitope masking immunofluorescence microscopy analysis and tests to induce lytic replication using the B95–8 cell line. ResultsIn this study, we analyzed high-resolution epitope-specific serum antibody levels in AD, revealing significant disparities in antibodies targeting multiple epitopes between the AD and control groups. Particularly noteworthy was the significant down-regulation of antibody (anti-DG#29) targeting an epitope of Epstein-Barr virus nuclear antigen 1 (EBNA1). This down-regulation increased AD risk in female patients (odds ratio up to 6.6), but not in male patients. Our investigation further revealed that the down-regulation of the antibody (anti-DG#29) is associated with EBV reactivation in AD, as indicated by the analysis of EBV VCA IgG or IgM levels. Additionally, our data demonstrated that the epitope region on EBNA1 for the antibody is hidden during the EBV lytic reactivation of B95–8 cells. ConclusionOur findings suggest a potential relationship of EBV in the development of AD in female. Moreover, we propose that antibodies targeting the epitope (DG#29) of EBNA1 could serve as valuable indicators of AD risk in female.

The influence of SARS-COV-2 viral infection on the serological level of igm antibodies in patients with infectious mononucleosis

Infectious mononucleosis (IM) is a disease caused by the Epstein-Barr virus (EBV), a member of the herpes virus family, which usually occurs in older children, adolescents, and young adults between the ages of 15 and 25. In young adults, infectious mononucleosis often causes fever, cough, pharyngitis and malaise, and lymphadenopathy. The similar symptoms of COVID-19 and EBV-induced IM suggest a possible association. The aim of this study is to investigate the possibility of coinfection with Epstein-Barr virus in COVID-19 patients. 80 serum samples from IM patients from January 2020 to December 2022 are included and analyzed by enzyme‐linked immunosorbent assay (ELISA) for diagnosis and determination of EBV-VCA IgM stage. Patients were classified into an EBV/SARS- CoV-2 coinfection group based on serologic results. A high frequency of reinfection and coinfection with EBV was found in patients with COVID-19 (23.42 % - 34.58 %). C-reactive protein (CRP) and aspartate aminotransferase (AST) results were higher in EBV SARS-CoV-2 coinfection during disease. EBV coinfection may be associated with disease severity at COVID -19.

The Impact of Epstein-Barr Virus Infection on Second Cancer Development in Newly Diagnosed Myeloma Patients Treated with Lenalidomide in the UK NCRI Myeloma XI Trial

Background Several factors have been linked to second primary malignancy (SPM) development in myeloma patients, including advanced age, immunocompromise and therapy, such as melphalan and lenalidomide (len). The impact of infection, including EBV is yet to be elucidated. Here we address this in the context of the UK NCRI Myeloma XI Trial for newly diagnosed transplant eligible (TE) and transplant non-eligible (TNE) patients. Methods Myeloma XI was a phase III, randomised, multi-centre, parallel group design, open-label trial comparing cyclophosphamide, thalidomide, len, carfilzomib and bortezomib induction combinations and len maintenance treatment in TE and TNE patients. TE patients received high dose melphalan supported by autologous stem cell transplantation (ASCT). Patients in both pathways were randomised to maintenance with len or observation. In total, 4358 patients entered. Planned SPM analysis was conducted in May 2019, with 318 patients developing an SPM prior to that point. Median follow-up from trial entry was 60 months (IQ range 47-76). A nested cohort analysis was performed to determine EBV infection and immunity status in 170 SPM patients for which serum samples were available. Forty-two trial patients who did not develop an SPM were used as a control group. EBV assessment time-points included pre-induction, post induction, 4 months post ASCT (TE only) and 1 year post induction. Peripheral blood serum samples were tested for EBV EBNA IgG Antibody/index (LIAISON®), EBV VCA IgM Antibody/Index (LIAISON®) and EBV positivity was determined using the artus® EBV RG PCR Kit from Qiagen. Active or recent EBV infection was evidenced by a positive EBV IgM antibody and/or EBV PCR. Results Of the 170 patients, 208 SPM were noted with 147 patients developing 1 SPM and 23 patients developing ≥2. One hundred and five patients developed an SPM following maintenance randomisation, with 76 receiving len and 29 being observed. The remaining 65 patients developed an SPM prior to maintenance. Eighty-four SPMs were diagnosed in 68 TE patients and 124 SPMs in 102 TNE patients. Of the 170 SPM patients, 8 had evidence of recent or active infection at the time of testing, evidenced by either IgM EBV antibodies (n=5), positive EBV PCR (n=2) or both (n=1). The median EBV DNA copies/ml was 353 (range 337-428). The median IgM antibody titre was 71.5U/ml (26 - >160). No patients in the control group had evidence of recent EBV infection (p=0.36). Of the 8 patients with evidence of EBV infection, 6 developed >1 SPM, Table 1. Five had been treated in the TE pathway, with all developing post maintenance randomisation, and 4 of the 5 receiving len maintenance. None of the 3 TNE patients received len maintenance, with 2 developing an SPM prior to maintenance randomisation. The median time from EBV testing to SPM diagnosis was 17·9 months (0.5-51.7). Two of the EBV positive patients developed a haematological SPM: myelodysplastic syndrome and Hodgkin lymphoma. Four patients developed a solid malignancy: lung, breast, ovary, and colon. The remaining cases were non-melanoma skin cancers, Table 1. Immune status (EBV IgG) was also determined. In TE patients, the median EBV IgG titre was 65.3U/ml at diagnosis (<3 - 600, n=48), falling to 28.1U/ml following induction (<3 - 326, n=41) and recovering to 44.2U/ml one year post ASCT (<3 - 600, n=22). In TNE patients, the median IgG titre at diagnosis was 39.1U/ml (<3 to 517, n=72), falling to 31.2U/ml 4 months post induction (<3 - 287, n=42) and recovering to 51.3U/ml after 1 year (<3 - 554, n=41). In the SPM patients the IgG EBV titres were noted to be <20U/ml in 5 of the 8 patients. Three of the eight patients had no detectable EBV IgG level (<3U/ml) Conclusions These data suggest that EBV infection is unlikely to be a risk factor for SPM development in myeloma patients. This is supported by the finding that EBV IgG titres were consistent with immunity in most patients (>20U/ml) and even in the patients with possible EBV infection, EBV DNA was only identified in 3 patients, and at a low level. In addition, the SPM developed are not classically associated with EBV infection or reactivation. It is noted that EBV infection status was not always determined at the time of SPM development. Despite this, the data does show that EBV immunity recovers following therapy, even in the post ASCT setting. EBV monitoring is therefore not supported by this work, although in patients who develop ≥2 SPM, further clarification is required.

Methicillin-resistant Staphylococcus aureus Bacteremia With Splenic Abscess Masked by Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis.

To the Editors: Splenic abscess, often associated with bacteremia, is a rare, potentially life-threatening disease that is sometimes reported in immunocompromised patients. It is characterized by prolonged fever and leukocytosis.1 Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is also a potentially life-threatening hyperinflammatory disease triggered by EBV infection and characterized by high-grade fever and cytopenia.2 We present a case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with splenic abscess masked by EBV-HLH. A previously healthy 7-year-old girl, with no family history of immunodeficiency or hematologic diseases, developed a fever, cough and rhinorrhea. She was treated for suspected bacterial pneumonia with clarithromycin followed by tosufloxacin. On day 4, blood examination showed bicytopenia (WBC 1690/μL, neutrophils 598/μL, platelets 92 × 103/μL) and a negative blood culture. On day 7, although the cough and rhinorrhea improved, the high-grade fever continued, and cracked lips, cervical lymphadenopathy and scattered erythema appeared. Blood examination showed hypercytokinemia (platelets 52 × 103/μL, C-reactive protein 13.63 mg/dL, fibrinogen 155 mg/dL, triglyceride 219 mg/dL, lactate dehydrogenase 5727 U/L). She was suspected to have HLH or Kawasaki disease and was referred to our hospital. We stopped antibiotic treatment and administered intravenous immunoglobulin 2 g/kg and prednisolone 2 mg/kg. Both ferritin (26,566 ng/dL) and soluble interleukin-2 receptor (4998/mL) were elevated, and along with fever, bicytopenia, and later-recognized splenomegaly, 5 of the 8 HLH 2004 diagnostic criteria were met.3 We did not perform bone marrow aspiration due to the invasiveness. Additionally, EBV-VCA IgM and EBV-VCA IgG were positive, and anti-EBNA was negative. The initial EBV infection was considered to be a trigger of the HLH. On day 8, bicytopenia and coagulopathy had improved, but C-reactive protein was further elevated. The blood culture and urine culture of day 7 were positive for gram-positive cocci, later identified as MRSA. On day 10, abdominal contrast-enhanced CT showed splenomegaly and multiple spleen abscesses (Fig. 1A–C). We administered intravenous vancomycin for 7 weeks (Figure, Supplemental Digital Content 1, https://links.lww.com/INF/E923). Repeated cardiac ultrasound showed no evidence of infective endocarditis. Since then, no relapse was documented.FIGURE 1.: Abdominal contrast-enhanced computed tomography on day 10. Splenomegaly, scattered nodular low-density areas (arrows) and multiple wedge-shaped low-density lesions (arrowheads) in the spleen (A, B, and C).No report has described bacteremia or splenic abscess after only 7 days following the onset of EBV-HLH. HLH causes severe neutropenia, which contributes to an immunosuppressed state.4 Splenic abscesses, sometimes with bacteremia, often occur in an immunosuppressed state.1,5 In our case, no etiology other than HLH, suggestive of immunodeficiency leading to a splenic abscess, was identified. HLH induces persistent high-grade fever and leukocytopenia.2,3 Furthermore, a study that reviewed 6 immunocompromised patients diagnosed with splenic abscesses reported that the five patients were febrile because of their splenic abscess and that none had leukocytosis.5 High-grade fever is the common characteristic of HLH and bacterial infection. Leukocytosis, one of the characteristics of bacterial infection, can be masked by leukopenia due to HLH, as in our case. In conclusion, a severe bacterial infection such as bacteremia with a splenic abscess may develop shortly after EBV-HLH. HLH induces persistent high-grade fever and leukocytopenia, and thus a diagnosis of concurrent bacterial infection may be challenging. Blood cultures and abdominal contrast-enhanced CT should be performed.

Primary Epstein-Barr Virus Infection in Healthy Children in Saudi Arabia: A Single Hospital-Based Study.

Primary Epstein-Barr virus (EBV) infection presents typically with features of infectious mononucleosis (IM) but it may present with atypical symptoms. We aim to evaluate the epidemiological, clinical and laboratory characteristics of primary EBV infection in children in western Saudi Arabia. A retrospective analysis of the electronic data of all children who were admitted to the hospital and were tested for EBV-viral capsid antigen (VCA) IgM in the period from 1 January 2018 to 31 December 2019. All data of the children with positive EBV-VCA IgM were collected. Patients were divided into two groups; IM and the non-typical presentations groups. Fort-two patients had positive EBV-VCA IgM; 71% had IM and 29% had non-typical presentations. IM was more common in early childhood (46.7%). The non-typical presentations were more in infants below 1 year (50%). Adolescents were less affected (6.7% and 16.7%, respectively). Time to diagnose EBV in the non-typical presentations group was longer than IM group; [3.4 (3.2-4.6) vs. 4.7 (4.1-5.5), p = 0.039]. The total leucocytes count was higher in the IM syndrome group compared to the non-typical presentation group [11 (10.3-17.7) vs. 5.5 (4.5-6.4), p < 0.0001]. Primary EBV infection in healthy children in Saudi Arabia occurs more frequently in the younger age groups. IM syndrome occurs more frequently in early childhood. The non-typical presentation occurs more frequently in infants. While adolescents are less commonly affected by primary EBV.

Evaluating commutability of EQA samples for epstein-barr virus serology

Background: Providing ‘patient-like’ commutable samples is an ongoing challenge for all EQA providers. RCPAQAP sources human serum and plasma from commercial suppliers, donated de-identified pools and consenting donors. For some assays plasma is not the recommended specimen type for testing. Aim: In 2019, RCPAQAP performed plasma to serum conversion for EBV surveys previously distributed as a plasma sample to investigate the effect of sample type on results. Methods: A single source plasma sample (from Physicians Plasma Alliance collected in sodium citrate) was distributed for two EBV surveys. RCPAQAP subsequently performed a plasma to serum conversion using an in-house method and redistributed the defibrinated sample for a third survey. A comparison of the replicate samples was performed to identify any discrepancies. Results: A shift in reporting for qualitative results (positive/negative) for EBV VCA IgM was noted over the three surveys. The two surveys using plasma samples had less than 80% agreement across methods whereas a consensus of 90% was achieved for the defibrinated sample. Discussion: There are many contributing factors that can lead to variation in results including sample type. For serological testing, it is important to be aware of any limitations for the assay in use. RCPAQAP now routinely defibrinates plasmas where required to improve the commutability of the sample.

Evaluation of the frequency and the relationship between EBV VCA IgM positive and EBV VCA IgG positive and serum level of 25 (OH) D3 in patients with CIS

Evaluation of the frequency and the relationship between EBV VCA IgM positive and EBV VCA IgG positive and serum level of 25 (OH) D3 in patients with CIS

Can we differentiate malignant peripheral nerve sheath tumor from benign neurofibroma without invasive sampling

One of the most important benign tumors in neurofibromatosis type 1 (NF1) is plexiform neurofibroma, and there is a risk of developing malignant peripheral nerve sheath tumor (MPNST) throughout life approximately 10%. However lesion characterization by anatomical imaging methods are not possible. Because of that most of cases goes to biopsy. Using of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) for lesion characterization can be helpful in NF1 patients. We aimed to present an example of the efficacy of FDG-PET/CT in distinguishing benign neurofibroma from MPNST. A 6-year-old male patient who had NF1 admitted to emergency service due to high fever. Acute upper respiratory tract infection was diagnosed; antipyretic and abundant fluid intake was suggested. When high fever continued, the patient referred to our hospital on detection of axillary lymphadenopathy. Leukocytosis was detected in patient's blood count. Sedimentation was 54 mm/h, C-reactive protein 166 g/L, and lactate dehydrogenase 276U/L. Blood and throat cultures did not show pathogenic bacteria. In serological tests, VZV-IgG, EBV-VCA-IgG, and CMV-IgG were avidite positive; Hepatitis B Ag, Anti-HIV, Anti-HAV IgG and IgM, Anti-HCV, EBV-VCA IgM, and VZV-IgM were negative. Based on these results, cervical and thoracic contrast-enhanced computed tomography was performed on preliminary diagnosis of MPNST. Solid lesions with rounded margins, large one being 49 mm in size, that extend from superior mediastinum to posterior mediastinum, left axillary region, and left part of neck were detected, and they were surrounding the vascular structures. Since neurofibroma, MPNST, and lymphoma could not be distinguished, patient referred to FDG-PET/CT scanning. In FDG-PET/CT, highest lesion maximum standardized uptake value (SUVmax) was 1.5; SUVmax lesion/SUVmax liver 1.0, and SUVmax/ SUV mean liver 1.5. Biopsy from mediastinal and axillary region did not have LN structure and was positive for S-100 immunostaining, and patient was diagnosed as benign neurofibroma. We believe that there is no need for biopsy in lesions considered benign based on FDG-PET/CT parameters.

Evaluation of Antiserum Level of EBV-VCA Antibodies in Acute Attack in Patients with Multiple Sclerosis

Introduction: MS is considered as one of the most common causes of disability among young people. As no definite treatment has been recognized for this disease yet, the patients are confused due to the life struggles with regard to the chronic clinical conditions, influencing their quality of life and health. Thus, finding the factors exacerbating the MS and trying to eliminate these factors are crucial. Thus, this research was conducted to evaluate the antiserum level of EBV-VCA antibodies in acute attack in patients with multiple sclerosis. Method and materials: In this descriptive, cross-sectional research, 30 patients with multiple sclerosis admitted to neurologic clinic due to acute MS, were included. Anti-serum level of EBV-VCA antibodies was measured by ELISA method. Results: The research results revealed that out of total 30 patients, 3 patients (10%) had positive serum EBV-VCA IgM, 5 suspected cases (16.7%) were doubtful and 22 patients (73.3%) were negative in this regard. No significant relationship was found between serum level of EBV-VCA IgG and acute MS attack (P>0.05). Conclusion: The results of the research and comparison of these results with those of some other studies suggest that there is no significant relationship between serum level of IgM EB-VCA and acute attack of multiple sclerosis.

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

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

Epstein-Barr virus infection and type I interferon signature in patients with systemic lupus erythematosus.

Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays. The EB virus DNA load was detected by real-time quantitative polymerase chain reaction. Peripheral blood mononuclear cells both from patients and controls were isolated immediately. The mRNA from these samples was subjected to real-time PCR for the latent genes EBNA1, EBNA2 and LMP1 of EB virus, as well as four IFN-stimulated genes (ISGs) ( OASL, MX1, ISG15 and LY6E). The antibody results were used to determine the stage of EBV infection (lytic, latent, or previous). Results SLE patients had a higher rate of lytic infection defined as positive EBV-VCA IgM antibody (39.66% vs 10.53%, p = 0.027), but not the EB virus DNA load. Patients with lytic EB virus infection had higher SLEDAI scores than patients with non-lytic infection (15.24 ± 2.63 vs 13.79 ± 3.24, p = 0.012). LMP1 was the only EBV gene that had a higher expression level in SLE patients than in healthy controls (3.26 ± 2.95 vs 1.00 ± 2.89, p = 0.000). It was also positively correlated with SLEDAI scores ( r = 0.462, p = 0.000). Levels of IFNα and the four ISGs were all significantly higher in SLE patients than in healthy controls ( p < 0.05). LMP1 was positively correlated with the four ISGs ( r = 0.403 ∼ 0.494, p < 0.05) in SLE patients but not in healthy controls ( r = -0.153 ∼ 0.129, p > 0.05). Neither EBNA1 nor EBNA2 was correlated with the ISGs in SLE patients or in healthy controls. Conclusions The SLE patients had higher rates of lytic EB virus infection and higher latent gene LMP1 expression, which might be associated with the development and/or the progression of SLE via the type I IFN pathway. The underlying mechanism needs more study.

Epstein-Barr Virüs Enfeksiyonunun Nadir Görülen Bir Komplikasyonu: Miyoperikarditli Bir Olgu Sunumu

Acute myocarditis usually develops after viral infections and is often asymptomatic. However, pericarditis can accompany it. Myopericarditis due to Epstein-Barr virus (EBV) infection is very rare. A 16-year-old male presented with severe chest pain. Cardiac enzymes were elevated and electrocardiographic examination revealed widespread decreased voltage and ST-T changes on the DII, DIII, aVF, V5, and V6 leads. Left ventricular systolic functions were normal and pericardial effusion was present on echocardiographic evaluation. EBV-VCA IgM and EBV-PCR were positive; EBV myopericarditis was diagnosed in the patient. The patient responded well to intravenous immunoglobulin (IVIG) and nonsteroidal antiinflammatory therapy and recovered completely. Myopericarditis should be considered in the differential diagnosis while evaluating patients with chest pain. The Epstein-Barr virus should be kept in mind even though it rarely causes myopericarditis.

THE ASSOCIATION OF EPSTEIN-BARR VIRUS ANTIBODIES WITH RHEUMATOID ARTHRITIS AMONG YEMENI PATIENTS IN SANA’A CITY

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with progressive disability, systemic complications and early death. Etiology of RA is unknown. It is assumed that environmental factors initiate RA development in genetically susceptible individuals. Epstein- Barr Virus (EBV) stimulates polyclonal B cell activation and has been suggested to play a role in RA pathogenesis. Current study aimed to study the association between EBV and RA. Methods: One hundred and sixty subjects were enrolled in the study. Eighty individuals were clinically diagnosed to have RA and confirmed by anti-CCP3 test. The remaining 80 individuals were healthy controls matched for age and sex. Serum IgG and IgM antibodies against EBV viral capsid antigen (VCA) were tested by an enzyme-linked immunosorbent assay (ELISA). Results: The crude prevalence rate of EBV-VCA IgM antibodies among patients was (21.2%) while in healthy individuals was (8.7%) with significant OR equals to 2.8 times for RA patient's. The female prevalence rate of EBV-VCA IgM antibodies was (21.8%) higher than of male (18.7%). The female prevalence rate of EBV-VCA IgG antibodies was (95.3%) higher than of male (75%). EBV-VCA IgG and IgM antibodies titers were elevated in RA patients than in healthy controls. However, the causative relationship between EBV and RA is complex and involves different mechanisms. Conclusion: In conclusion, high titers of EBV antibodies are associated with RA. However, the causative relationship between EBV and autoimmune diseases is complex and involves different mechanisms. Peer Review History: Received 16 August; Revised 28 August; Accepted 5 September, Available online 15 September 2017 Academic Editor: Dr. Amany Mohamed Alboghdadly, Princess Nourah bint abdulrahman university, Riyadh, amalbgadley@pnu.edu.sa UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Mujde Eryilmaz, Ankara University,Turkey, meryilmaz@ankara.edu.tr Dr. Tamer Elhabibi, Suez Canal University, Egypt, tamer_hassan@pharm.suez.edu.eg Similar Articles: SEROPREVALENCE OF ANTI-MANNOSE BINDING LECTIN AUTOANTIBODIES IN PATIENTS WITH RHEUMATOID ARTHRITIS IN SANA'A CITY- YEMEN

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OBJECTIVES/SPECIFIC AIMS: Allostatic load, the chronic stress-induced wear and tear on the body, has a cumulative deleterious effect in individuals over their lifetime. Recent studies have suggested that socio-economic status, psychological determinants, and biomedical health cumulatively contribute to allostatic load in young adults. Although these finding individually suggest that African American children may be particularly susceptible to the effects of allostatic loading due to racially-based discrimination and economic instability, few studies have shown the effect of exposure to violence on the allostatic load carried by young African Americans. METHODS/STUDY POPULATION: The Biological and Social Correlates of Drug Use in African American Emerging Adults (BADU) data set is composed of young African Americans (n=557 individuals) living in the Washington, DC area, collected from 2010 to 2012. Study participants were sought equally between males and females (n=283, n=274, respectively). This data set provides a rich source of information on the behavioral, mental, and physical health of African American young adults (18–25 year olds) living in the Washington, DC area. Analysis of 6 biomedical markers were measured in BADU study participants: C-reactive protein, cortisol, Epstein-Barr virus IgG, IgE, IgA, and IgM, known to be markers of immune stress and allostatic load. Naive Bayes was used to identify participant responses that were correlated to elevated stress biomarker levels. RESULTS/ANTICIPATED RESULTS: Violence was most closely correlated to elevated EBVVCA IgM and IgE levels. Elevated IgE levels correlated to increased experience of familial violence and sexual abuse; familial drug abuse and depression; violence and community violence. Cortisol is positively correlated to reported emotional state (R=0.072) and perceived individual discrimination (R=0.059). DISCUSSION/SIGNIFICANCE OF IMPACT: Allostatic load appears to be high in individuals who self-report exposure to violence. Both perceived mental health and violence were correlated to elevated stress biomarkers. When Epstein-Barr virus viral capsid antigen IgM was compared with violence features characterized in the data set, we found that internalization of environmental stressors were most strongly correlated to elevated allostatic load markers. This work suggests that internalization of experienced violence may be as important as the actual violence experience.

Rare Case of Patient with HIV Related Plasmablastic Lymphoma Presenting with Bilateral Parotid Involvement and Hypergammalobulemia

44 year old male with no past medical history presents with rapidly enlarging neck mass over past two months. He denied B-symptoms. Clinical examination revealed bulky midline neck mass with bilateral cervical and left supraclavicular adenopathy. 6/29/16 excisional lymph node biopsy of neck lymph node showed a monomorphic proliferation of malignant cells with large immunoblastic tumor cells with prominent nucleoli (Figure1). Neoplastic cells expressed MUM-1, CD138 (Figure 2), and were lambda light chain restricted. Neoplastic cells were negative for CD20, CD79, CD3, CD5, CD7, and BCL-2. Additionally, Cyclin D1, BCL-6, CD30, ALK-1, S100, CD56 was negative. Ki-67 was 99%. EBER by ISH was positive (Figure 3). Karyotype was normal. PET CT 7/1/16 Showed small hypermetabolic lymph nodes in the right neck, bilateral parotid gland with additional hypermetabolic activity in the left supraclavicular fossa and central neck base along with activity in the tongue base with maximum SUV 16.1. CT neck chest abdomen and pelvis 7/1/16 showed bilateral enhancing parotid lesions, large central midline neck mass with right strap muscle involvement. Also, there was soft tissue prominence of the adenoids, tonsil pillars, lingual tonsils, laryngeal ventricle. Last there was bilateral deep cervical, supraclavicular, & posterior cervical lymphadenopathy. Lumbar puncture, bone marrow biopsy, & MRI brain were negative for involvement. Labs 6/27/16: Platelet 126 10x3/µL, hemoglobin 15.7 g/dL, white blood cell 5.2 with variant lymphocytes. Uric acid 4.3 m/dL, total protein 9.3 g/dL, creatinine 1.23 m/dL, alanine aminotransferase 83 U/L, aspartate aminotransferase 83 U/L and complete metabolic panel otherwise normal. LDH 228 U/L, beta 2 microglobulin 4.5 mg/L. HIV-1 test was positive with 94316 copies/mL by PCR. CD4 count 65 cells/mcl. EBV VCA IgM <0.2 AI, EBV VCA IgG > 8.0 AI. IgG 3023 mg/dL, IgE 207IU/ML, IgA 581 m/dL, IgM 286 mg/dL, free kappa 117 mg/L, free lambda 97.94 mg/L and normal kappa/lambda ratio. SPEP with immunofixation consistent with inflammatory response. Peripheral blood flow cytometry revealed a minimal kappa predominant monoclonal B-cell population. Patient started on DA-EPOCH with prophylactic intrathecal methotrexate with excellent clinical response after first cycle. Plan for 4-6 cycles with prophylactic intrathecal chemotherapy followed by autologous stem cell transplantation. For supportive care, the patient was started on HAART therapy, acyclovir, fluconazole, Levaquin, azithromycin. To our knowledge this is the first case of bilateral parotid gland involvement in PBL. Furthermore it is unclear if the hypergammaglobulinemia is related to HIV infection vs. directly PBL related. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Seroprevalence and real-time PCR study of Epstein—Barr virus and the value of screening in pretransplant patients

This study was performed to estimate the prevalence of Epstein–Barr virus immunoglobulin M virus capsid antigen (EBV IgM VCA) among healthy blood donors and to confirm the real risk of transfusion transmission by detection of virus load using PCR quantification. A total of 860 apparently healthy Egyptian blood donors were enrolled and tested for EBV IgM VCA. Quantitative PCR was performed for reactive cases for EBV IgM VCA. An overall 38 patients were reactive for EBV IgM VCA, constituting 4.4% of the sample. Reactivity of Epstein–Barr virus did not differ significantly as regards sex distribution, blood grouping, Rh factor positivity, and hemoglobin level, but it was significantly higher among upper Egypt participants than among those from other regions (P = 0.006). There was a very high statistically significant positive correlation between the titer of EBV VCA IgM reactive cases and age in the studied group (P = 0.0001 and r = 0.6). PCR was negative for all of the reactive cases. Routine screening for Epstein–Barr virus in blood bags is not economical. Screening is highly recommended only for immunocompromised and pretransplant patients. Viremia is not the role in individuals with EBV IgM positive sera, which in turn changes some concepts in organ transplantation.

Splenic Infarct: A Rare Presentation in a Pediatric Patient

A previously healthy 16-year-old male presented with a two day history of persistent epigastric pain. His physical examination was significant for tenderness in the left hypochondriac region with a palpable spleen 2cm below the left sub-costal margin. A CT scan of the abdomen showed a splenic infarct. Heterophile and EBV VCA IgM antibody test were positive. This is a rare case of infectious mononucleosis presenting with splenic infarct in an adolescent male without co-morbidities.

Effect of high dose vitamin C on Epstein-Barr viral infection.

BackgroundMany natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection.Material/MethodsThe data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection.ResultsOur data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels.Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease.In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.ConclusionsThe clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.

Evaluation of Clinical and Laboratory Findings of Pediatric Patients with Adenovirus-Associated Respiratory Tract Infections

Upper respiratory tract infections caused by adenoviruses present long lasting fever for five days and elevated acute phase reactant levels. They are generally misdiagnosed as bacterial infections and are mistreated with antibiotics. The diagnosis of adenovirus infections mainly depends on direct antigen tests, virus isolation and detection of viral DNA using polymerase chain reaction (PCR). The aim of this study was to evaluate the clinical and laboratory findings of the children diagnosed as adenoviral respiratory tract infection by multiplex PCR (mPCR). A total of 27 children (18 male, 9 female; age range: 1-7 years, mean age: 4.4 years) whose nasopharyngeal swab samples were found positive for adenovirus DNA with a commercial mPCR method (Seeplex® RV15 ACE Detection Kit, Seegene Inc, Korea) were included in the study. The throat cultures of the patients revealed no bacterial pathogens and EBV VCA-IgM antibodies were negative. The clinical and laboratory data of the children with long lasting high fever diagnosed as adenovirus infection were evaluated retrospectively in terms of their complaints on admission, symptoms detected in physical examination, laboratory findings and therapy protocols. The patients were categorized according to hospitalization period (< 3 days or ≥ 3 days) and also according to the symptoms compatible with upper or lower respiratory tract infections. The quantity of clinical symptoms (≤ 2 or > 2) and the presence of upper or lower respiratory tract findings were evaluated if there were a difference by means of hospitalization rate and period. The most common complaint of the patients with adenoviral respiratory diseases was fever (27/27; 100%), and the most common admittance season was april-may-june period (20/27; 74%). The mean temperature was 38.4°C (range: 38-39.8°C) and the fever continued for 1-5 days after hospitalization. The most common physical examination finding was tonsillary hyperemia and hypertrophy (63%), followed by lower respiratory tract disease symptoms (37%), otitis media (14.8%), conjunctivitis (7.4%), and rash (3.7%). Laboratory tests could be performed for 24 cases and 95.8% of them yielded high CRP level, 87.5% high sedimentation rate, 62.5% neutrophilia, 33.4% leukocytosis and 20.8% lymphocytosis. It was noticed that 85.2% (23/27) of the patients were under antibiotic treatment on admission. Twenty-three patients (85.2%) were hospitalized, and the duration of hospitalization was between 1-8 (mean: 3.78) days. When the hospitalization rate was evaluated in terms of different measures, it was found that the rate was 81.8% (18/22) in patients with ≤ 2 symptoms, 100% in patients with > 2 symptoms (5/5); 100% (10/10) in patients with lower respiratory tract disease symptoms; 100% (15/15) in patients with neutrophilia, 88.2% (15/17) in patients with CRP levels of ≥ 2.8 - < 100 mg/L, and 100% (6/6) in patients with CRP levels of ≥ 100 mg/L. Neutrophilia and high CRP levels were found to be the main factors related to the hospitalization rate (p< 0.05). In conclusion, adenoviral etiology should be determined by a rapid and sensitive laboratory method such as mPCR, in cases with tonsillopharyngitis who exhibit leukocytosis, neutrophilia and high CRP levels and no bacterial pathogens in throat culture, in order to prevent unnecessary antibiotic use and hospitalization.

A CASE OF ACUTE CEREBELLAR ATAXIA DUE TO EPSTEIN–BARR VIRUS AND REVIEW OF THE LITERATURE

BackgroundThe differential diagnosis of acute cerebellar ataxia in a young adult includes vascular, inflammatory, toxic, neoplastic, paraneoplastic, genetic and infective causes. Neurological complications of EBV are rare, but include Acute...