VCA IgG Research Articles

Seroepidemiological study of Epstein-Barr virus infection in reproductive age women in Bulgaria

Abstract Background At the present stage, studies on the involvement of Epstein-Barr virus (EBV) in neonatal pathology are rare. Establishing seroprevalence among women of reproductive age has important epidemiological significance in order to determine the risk of infection during pregnancy and intrauterine infection of the fetus. The aim of the study is to determine the seroepidemiological status of EBV in reproductive age women. Methods We conducted a prospective seroepidemiological study in which 96 healthy women of reproductive age (18 to 49 years) were tested during the period December 2023 - January 2024 in Medical Center “Clinical Institute for Reproductive Medicine”- Pleven, Bulgaria. Participants were surveyed on a voluntary basis. The exclusion criteria were: presence of autoimmune disorder, immunosuppressive states, malignancy and populations at risk such as persons under 18 years of age and pregnant women. The presence of specific antibodies were detected using a standardized Anti-EBV VCA IgM, Anti-EBV VCA IgG and Anti-EBV EBNA-1 IgG ELISA kits. The demographic and anamnestic data were collected for each participant in Case Report Form. Results The average age of the women was 34.41±5.44 years. Dominating were women with higher education (76.04%) living in urban areas (91.67%). The results of the seroepidemiological study of markers for EBV show that 98.96% of women of reproductive age are seropositive. There was no significant correlation between the presence of antibodies and socio-demographic indicators (living area, education and number of family members). Conclusions The results of this study imply that only 1.04% of the reproductive age women in Pleven region are susceptible to infection with EBV. Although interpretation of the serological status indicates a low risk of primary infection, active monitoring of high-risk groups pregnant women is necessary because of the possibility of EBV reactivation. Key messages • On-going monitoring of the seroepidemiological EBV status in reproductive age women is necessary to determining the possibility of EBV reactivation and to reduce the teratogenic risk of the infection. • Seroepidemiological surveillance of markers for EBV infection in reproductive age women is part of effective preventive measures at the public health level.

Investigation of atypical serological profiles for Epstein-Barr virus (EBV)

BackgroundCommercial immunoassays that detect IgG and IgM directed toward VCA and IgG EBNA are used in combination to assess EBV immune status. However, this strategy does not always confirm/exclude recent/past EBV infection or absence of immunity. ObjectivesThe aim of our study was to perform complementary investigations on samples with atypical EBV serological profiles, in order to identify the clinical situation they correspond to. Study designEBV serology was performed using EBV VCA IgM/IgG and EBNA IgG LXL® DiaSorin assay. Complementary investigations included ELISA IgM VCA, immunoblots, CMV IgM/IgG and CMV IgG avidity, and EBV PCR. ResultsIn our study, 12810 EBV serological results were analyzed, and 3580 atypical profiles were detected (28 %). Among these latter, isolated VCA IgG represented 42.9 %, the three positive markers accounted for 29.1 %, isolated EBNA IgG represented 18.5 %, isolated VCA IgM accounted for 6.4 % and positive VCA IgM & positive EBNA IgG represented 3.1 %. VCA IgG detected alone were specific in 100 % cases and EBNA IgG detected alone were specific in 91.7 % cases. VCA IgM detected alone were false positive or due to a cross reaction with CMV in 52.8 % cases. The pattern positive VCA IgM and positive EBNA IgG correspond to a false positive in VCA IgM, EBNA IgG or both in 83.4 % cases. Positive EBV VCA IgM/IgG and EBNA IgG were unreliable to detect active EBV infection in 66.7 % cases. DiscussionAtypical EBV serological profiles may correspond to several clinical situations and complementary investigations allow to determine the immune status in more than 98.5 % cases.

A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression.

Although fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders. The main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up. A retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed. A total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0). MS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.

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.

P309 Impact of EBV Status on decision making for advanced therapies in IBD Patients

Abstract Background The CESAME study suggested that Thiopurines confer increased risk of lymphomas in IBD patients who are naïve to Epstein - Barr virus (EBV) particularly in young males. European Crohn’s and Colitis Organisation (ECCO) guidelines recommend considering EBV screening in individuals prior to initiating immunomodulator therapy. The impact of EBV serology status on decision-making processes regarding advanced therapies in IBD patients is not studied before. Methods Consecutive patients initiated on advanced therapies (biologics or small molecules). EBV nuclear and vca IgG status were recorded. The first advanced therapy of the positive and negative patients were compared. Proportion of the negative patients who seroconverted and the time to seroconversion were analysed. Results We included 491 patients (M: F 1:14). Median age of patients who had EBV serology done prior to initiating on advanced therapies was 31.5 years (range 5-84 years) .In 41 (8.35%) patients, neither nuclear nor vca IgG antibody were detected at initial screening. The median age of EBV negative patients was 26 years (range 13-51 years).30 of the EBV negative patients were males. Azathioprine/6MP was not initiated in 37 (90.24%) of the EBV negative patients. Re-testing of EBV negative patients were done at a median interval of 28 months (range 3-90 months). 5 of these retested patients (12.2%), seroconverted and in three of this patients Azathioprine was used following seroconversion. Conclusion A significant minority of IBD patients are EBV negative when tested as part of pre biologic screening, including in male patients above the age of 25. Thiopurine therapy was avoided in these patients. Only a fraction of EBV negative patient seroconverted on re-testing. The impact of EBV testing in treatment decision, as well as the attributable costs needs to be evaluated further.

Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response.

Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler's murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection in vitro. 1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide. A total of 101 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 80 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L). Antiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3. Treatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response.

High Epstein-Barr virus capsid antigen IgG level associates with the carriership of CD8+ T cell somatic mutations in the STAT3 SH2 domain

High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors, without difference between multiple sclerosis (MS) patients and controls. Here we tested whether anti-viral antibodies associate with the carriership of these mutant clones. We compared antibody responses against common viruses in mutation carriers vs. non-carriers. Plasma samples of 152 donors (92 MS patients, 60 controls) were analyzed for antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6A and parvovirus B19. The mutation carrier status associated with EBV VCA IgG level (p = 0.005) and remained significant after logistic regression (p = 0.036). This association was contributed similarly by MS patients and controls. These results suggest that EBV contributes to the generation or growth of these clones. The pathogenic role of the STAT3 mutant clones in MS is presently unclear, but their detailed characterization warrants further study.

Epstein-Barr Virus and multiple sclerosis in a Spanish cohort: A two-years longitudinal study.

Objectives1. To analyze the prevalence and levels of anti-EBNA-1 and anti-VCA IgG antibodies of Epstein-Barr virus (EBV) in a Spanish cohort of multiple sclerosis (MS) patients and their interactions with other environmental and genetic risk factors. 2. To analyze the association of the evolution of these antibodies with the clinical response to different disease modifying therapies (DMTs) after two-years of follow-up. 3. To assess their possible correlation with the class II HLA alleles as well as with several SNPs identified in GWAS related to disease susceptibility.Materials and methodsWe recruited 325 MS patients without DMT (serum samples were collected 1-3 months before starting a therapy) and 295 healthy controls (HC). For each patient we also collected serum samples 6, 12, 18 and 24 months after starting the DMT. EBNA-1 and VCA IgG titers were analyzed by ELISA; 25(OH)D levels were analyzed by immunoassay; HLA DRB1*15:01 allelic variant was analyzed by Taqman technology.Results1. 97.8% (318/325) vs. 87.1% (257/295) positives for EBNA-1 in MS patients and HC, respectively (p<0.0001; O.R. = 6.7); 99.7% (324/325) vs. 94.6% (279/295) for VCA in MS patients and HC, respectively (p=0.0001; O.R. = 18.6). All MS patients were positive for EBNA-1 and/or VCA IgG antibodies vs. 280/295 (94.9%) HC (p<0.0001). IgG titers were also significantly higher in MS patients than in HC. 2. We did not find any statistical correlation in the variation of the EBNA-1 and VCA IgG titers between baseline and 24 month visits with the number of relapses, progression, clinical response, NEDA-3 condition or therapeutic failure. 3. When we compared different epidemiological and clinical variables between those with genetic factors associated with lower EBNA-1 IgG titers and all other MS patients, we found MS started 3.5 years later among the first.ConclusionsThese results confirm that MS occurs rarely in absence of EBV. An intriguing association between genetic burden and lower EBNA-1 IgG titers was associated with an earlier age of disease onset. Similar studies with B-cell–targeted therapies should be performed.

Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature

BackgroundAcute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.Case presentationA 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.ConclusionsAcute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.

Declining Epstein-Barr Virus Antibody Prevalence in College Freshmen Strengthens the Rationale for a Prophylactic EBV Vaccine

Background: To better understand the epidemiology of primary Epstein-Barr virus (EBV) infection and to identify EBV-naïve candidates eligible to receive a prophylactic EBV vaccine, we screened freshmen from the University of Minnesota Class of 2025 for circulating EBV antibody, which is indicative of previous infection. This permitted us to compare their EBV antibody prevalence with that of 4 other freshman classes (Classes of 2010, 2011, 2016, 2021) that have been previously published. Methods: Freshman students were recruited during screening sessions in the residence halls. Venous blood was collected and the serum fraction tested for IgG antibody against EBV viral capsid antigen (VCA IgG) using commercial enzyme immunoassays. Results: All classes combined, 1196 participants were tested (female, 677; male, 513; did not identify gender, 6) who were 18–23 years old (median, 18; mean, 18.37). The EBV VCA IgG antibody prevalence was 58% (689/1196) and was higher in women than men. The EBV antibody prevalence of 64% (170/267) in the 2010 freshman class versus 52% (78/150) in the Class of 2025 was statistically significantly different (p = 0.0223, Fisher exact test).” Conclusions: Sufficient participants are available for a prophylactic vaccine trial. Antibody prevalence decreased over 15 years from 64% to 52%. If this trend continues, the number of EBV-naïve adolescents and young adults who are in the age group most susceptible to infectious mononucleosis will increase, strengthening the rationale to develop an effective prophylactic EBV vaccine.

Differences in serological profiles of Epstein-Barr virus infection in patients with head and neck tumors and lymphomas.

e18055 Background: Epstein-Barr virus (EBV) is associated with the development of various cancers, including nasopharyngeal carcinoma (NPC), gastric cancer, and lymphomas. The use of EBV serological markers in screening and monitoring of NPC has been shown to be valuable. The significance of serological markers in the diagnosis of other head and neck cancers is poorly described. The aim of this study was to analyze the serological profiles of EBV infection in patients with head and neck tumors. Methods: The main group included 24 patients with laryngeal cancer (n = 12) and oral mucosa cancer (n = 12). Keratinizing squamous cell carcinoma was registered in 22 (91.7%) patients, and adenoid cystic cancer in 2 (8.3%) patients. The control group included 44 lymphoma patients. Antibodies to EBV proteins were determined in the blood serum by ELISA and Western blot (WB) tests. Results: ELISA detected antibodies of the A, M and/or G classes against various EBV proteins in 100% of patients in the main group and 97.7% of controls. IgA VCA in patients with head and neck cancer were determined 2.7 times more often (50% vs 18.2%, p = 0.034) than in patients with lymphomas, IgG EA - 2.1 times more often (58.3% vs 27.3%, p = 0.049), and the complex of acute infection markers (IgA VCA, IgM VCA, IgG EA in various combinations) was determined 2.0 times more often (66.7% vs 34.1%, p = 0.045). Atypical profile (only VCA IgG+) was determined only in patients with lymphomas (4.5%). The profile characteristic of immunosuppression (IgG VCA+, IgG EA+, NA IgG±) was determined 1.8 times more often in patients with head and neck cancer than in patients with lymphomas (25% vs 13.6%, p &gt; 0.05). According to WB tests, patients of the main group more often demonstrated IgM EBNA-1p79 (16.7%), VCA p65 (16.7) and p22 (16.7%), while controls – VCA p22 (27.8%), EA-R p93 (16.7%) and VCA p33 (16.7%). IgG in the main group was more often determined to EBNA-1 p79 (91.7%), VCA p22 (91.7%) and VCA p33 (66.7%), in the control group to VCA p40 (87.5%), EBNA-1 p79 (75%) and VCA p22 (62.5%). Statistically significant differences were found only for VCA p42 (0% in the experimental group and 37.5% in controls, p = 0.049), VCA p40 (25% and 87.5%, p = 0.009) and p27 (0% and 37.5%, p = 0.049). EA-D p45 was determined only in patients with lymphoma. Conclusions: The vast majority of patients in both groups were previously infected with EBV. Serological profiles of EBV infection in patients with head and neck cancer and lymphomas were significantly different. Markers of acute infection were more often determined in patients with head and neck cancer; the range of individual proteins in the main group was narrower than in the control group. The biological meaning of the differences in the detection rates of antibodies to individual EBV proteins in patients of the two groups remains to be elucidated.

Application of magnetic immunofluorescence assay based on microfluidic technology to detection of Epstein-Barr virus

EB病毒(Epstein-Barr virus, EBV)的早期诊断能够降低患者发生重大疾病的风险。临床上常用的EBV抗体的检测方法存在耗时长、试剂消耗大和效率低等缺点。相比于传统的检测方法,微流控(microfluidics)技术具有高通量、试剂消耗少,污染少和自动化程度高等优点,磁免疫荧光技术具有检测效率高、信号强等优点,将两者的优势结合,能够弥补传统方法的不足。鉴于此,采用聚甲基丙烯酸甲酯(PMMA)作为芯片原材料,经过激光切割及真空热压加工工艺能够快速获得芯片。将包被抗原的磁珠及包被抗人抗体的荧光微球经过冷冻干燥工艺快速冻干成小球并嵌入芯片内,经过孵育和清洗后,进行检测。通过图像分析快速得到检测结果。通过精密度、特异性、剂量-反应曲线及检出限测试,进行性能验证。通过与化学发光免疫分析法(CLIA)检测的临床样本比对,进行方法学与临床应用评价。结果显示相对标准偏差(RSD)均小于10%。与多种常见的病原体抗体均无交叉反应。EB病毒衣壳抗原(Epstein-Barr viral capsid antigen, EB VCA)IgG项目的检出限为1.92 U/mL,线性范围为1.92~200 U/mL,阳性符合率为95.77%(68/71),阴性符合率为86%(43/50); EB VCA IgA项目的检出限为2.79 U/mL,线性范围为2.79~200 U/mL,阳性符合率为92%(46/50),阴性符合率为92.96%(66/71); EB病毒核心抗原1(Epstein-Barr nuclear antigen 1, EB NA1)IgG项目的检出限为3.13 U/mL,线性范围为3.13~200 U/mL,阳性符合率为92.96%(66/71),阴性符合率为92%(46/50); EB NA1 IgA项目的检出限为1.53 U/mL,线性范围为1.53~200 U/mL,阳性符合率为90%(45/50),阴性符合率为91.55%(65/71)。4个项目能在20 min内快速完成检测,且与临床上使用CLIA方法测试的结果具有良好的相关性,可以为临床提供一种快速、灵敏、简便、自动化程度高和易于基层推广的检测方法。

An Unusual Presentation of Glandular Fever

Epstein-Barr virus (EBV) is an ubiquitous DNA herpesvirus with >90% of adults >40 years of age showing a serological response. While in their youth, primary EBV infection may pass unnoticed, young adults have a high incidence of infectious mononucleosis (IM). This is characterized by a triad of pharyngitis, cervical lymphadenopathy, and fever because of a self-limiting lymphoproliferative disease. Common complications include but are not limited to hepatitis, splenomegaly, encephalitis, and haemophagocytic lymphohistiocytosis (HLH) with evidence that Caucasian males and smokers are more likely to suffer severe disease. Here we present a 21-year-old male who presented with a 2-week history of fever, dry cough, and a 4-week history of pharyngitis. He had no exposure to unwell contacts and denied any new sexual partners. Examination revealed general pallor with tender bilateral cervical lymphadenopathy and pharyngeal erythema. Admission bloods revealed pancytopenia (WCC 1.5 × 109/L, Plt 84 × 109/L, and Hb 82 g/L) with normal reticulocyte count and raised mean corpuscular volume (114 fL). Serum vitamin B12 and folate were low with serum ferritin raised (1027 µg/L) suggesting a proinflammatory state. Admission liver function tests, coeliac serology, autoimmune panel (ANA, ANCA, and anti-dsDNA), hepatitic (hepatitis A, B, and E), human immunodeficiency virus (HIV), toxoplasmosis, parvovirus, and CMV serology were normal. The monospot test on day 1 of the presentation was negative. Ultrasound (US) of the abdomen on day 3 of the presentation revealed isolated splenomegaly (16.8 cm). Day 4 EBV serology (VCA IgM, VCA IgG, and EBNA IgG) was negative as such haematological investigations including JAK2, serum free light chains, and BCR-ABL were undertaken alongside cervical lymph node core biopsy. Repeat Monospot testing on day 7 came back positive. Repeat EBV serology now showed equivocal EBV VCA IgG (0.77 OD) and positive VCA IgM (9.04 OD) with concurrent new hepatitis. Histopathology of the core biopsy revealed Sternberg-reed cells and a mixed immunoblastic reaction in keeping with resolving IM. This case highlights the need for physicians to have a strong clinical suspicion of IM and understand the multiple ways in which IM may be present as well as the time lag to positivity in serological testing.

Особливості ураження печінки при інфекційному мононуклеозі в дітей

У даний час спостерігається тенденція до зростання захворюваності на інфекційний мононуклеоз (ІМ). Мета дослідження — виявити клінічні особливості ураження печінки при ІМ у дітей. Матеріали та методи. Проаналізовано дані історій хвороби 42 дітей віком від 4 до 15 років із діагнозом хронічного гепатиту. Визначали активність аланінамінотрансферази, аспартатамінотрансферази, лужної фосфатази, гамма-глутамілтранспептидази, рівень білірубіну, маркери вірусних гепатитів. Проводили ультра­звукове дослідження, імуноферментний аналіз із визначенням у крові маркерів Епштейна — Барр вірусу (ЕБВ) (IgM VCA, IgG EA, IgG VCA, авідність) і цитомегаловірусу (ЦМВ) (IgM, IgG, авідність); ДНК-ЕБВ і ДНК-ЦМВ методом полімеразно-ланцюгової реакції. Виділено 3 групи: 1-ша група — хворі на ІМ ЕБВ-етіології (17 пацієнтів), 2-га група — хворі на ІМ ЦМВ-етіології (16 пацієнтів), 3-тя група — мікст-ІМ ЕБВ + ЦМВ (9 пацієнтів). Дані оброблені методами статистичного аналізу з використанням прикладної програми Statistica 6. Результати. У 85,7 % випадків ІМ перебігав у типовій формі із середнім ступенем тяжкості (збільшення розмірів лімфовузлів у 98,6 % хворих, тонзиліт — у 54,7 %, гепатомегалія — у 71,4 %, спленомегалія — у 38,1 %). Характерні зміни гемограми при ІМ: лейкоцитоз (64,2 %) і атипові мононуклеари (73,5 %). У 15 дітей (35,7 %) підвищені трансамінази. Жовтяничні форми гепатиту спостерігалися в п’яти пацієнтів. Рівень атипових мононуклеарів у крові понад 20 % відзначався в 43,3 % хворих. УЗД виявило дифузне підвищення ехогенності печінки в 36,6 % пацієнтів. Висновки: 1. Гепатит при ІМ виявлений більше ніж у половини хворих, його розвиток і вираженість корелюють з етіологічними особливостями захворювання (мікст-інфекція ЕБВ + ЦМВ, rs = 0,60 ± 0,07); віком (rs = 0,40 ± 0,07), статтю (rs = 0,80 ± 0,07). 2. Гепатит на фоні ІМ характеризується вірогідним переважанням безжовтяничних форм із помірним і короткочасним підвищенням трансаміназ, супроводжується спленомегалією й рівнем атипових мононуклеарів у крові понад 20 %.

Стан антивірусного імунітету у хворих на неалкогольний стеатогепатит учасників ліквідації аварії на Чорнобильській АЕС

Обстежені 34 особи чоловічої статі, які після участі в ліквідації наслідків аварії на Чорнобильській АЕС захворіли на неалкогольну жирову хворобу печінки (НАЖХП). Стан противірусного захисту оцінювали за рівнями антитіл класів IgG та IgM у сироватці крові. У більшості хворих на НАЖХП учасників ліквідації наслідків аварії на Чорнобильській АЕС виявлені антитіла класу IgG, але не IgM до персистуючої мікст-інфекції вірусами простого герпесу 1-го та 2-го типів, цитомегалії та вірусу Епштейна — Барр. Виявлено наявність позитивного кореляційного зв’язку між титрами антитіл до вірусів простого герпесу 1-го та 2-го типів і цитомегаловірусу (rs = 0,383, р = 0,040), а також між титрами антитіл до ядерного антигена вірусу Епштейна — Барр та антитіл до корового антигена вірусу Епштейна — Барр (rs = 0,584, р = 0,002) у хворих з персистуючою мікст-інфекцією цих герпесвірусів.

Epidemiological characteristics of Epstein–Barr virus infection

Introduction. The Epstein–Barr virus (EBV) is one of the most common pathogens — it infects 90% of the world’s population. However, specific characteristics of the EBV infection epidemic process remain unidentified. The previous studies focusing on assessment of incidence rates for infectious mononucleosis (IM) tend to ignore the serological status of the population.The aim of the study was to identify epidemiological characteristics and assess the prevalence of serological markers for EBV infection for further epidemic control measures development.Materials and methods. In Moscow, the thorough analysis was performed using the data on IM incidence (Form 2 "Data on Infectious and Parasitic Diseases") and test results for 138,232 people checked for presence of VCA IgG, EBNA IgG, VCA IgM, EA IgG, and EBV DNA in their blood and saliva in 2011–2020.Results. The periodic pattern of IM incidence was discovered, demonstrating the repetitive peaks every 9 to 11 years and a strong direct correlative relationship with detection rates for active EBV infection markers. The intra-annual dynamics of IM incidence is characterized by a seasonal upswing during cold seasons of the year, reaching its peaks in October, November, or February and associated with a marked decrease in the VCA IgG and EBNA IgG seroprevalence. Children within the 1 to 17-year age range are groups at risk for acquiring primary infection, demonstrating significantly lower detection rates for chronic EBV infection (VCA IgG and EBNA IgG) markers and higher rates for VCA IgM and EBV DNA markers in blood compared to adults. The contribution of adult population to the epidemic process is formed through reactivation of chronic infection, which is observed primarily among women.Conclusion. The identified characteristics are essential for comprehensive understanding of the EBV infection epidemic process and can be used for developing preventive and anti-epidemic measures.

S2731 Isolated EBV-Induced Acute Hepatitis in the Absence of Infectious Mononucleosis

Introduction: Epstein-Barr virus (EBV) is a globally prevalent herpesvirus with an estimated 90-95% seropositivity rate worldwide. It is most known for causing infectious mononucleosis characterized by the classic triad of fever, pharyngitis, and lymphadenopathy. Hepatitis is a common manifestation seen in 90% of cases;however, isolated acute hepatitis in the absence of infectious mononucleosis is a rare clinical presentation. Case Description/Methods: An 18-year-old female with no medical history presented with fevers, fatigue, myalgia, and headache ongoing for one week. She had been evaluated previously with recommendations for supportive care for an unspecified viral illness. Workup at the time had been negative for urine hCG, COVID-19, heterophile antibody, Lyme disease, and bacteremia. However, symptoms worsened with the development of nausea, vomiting, and darkening of her urine. Prior to this, patient had been in her normal state of health without sick contacts, travel history, animal exposures, risky sexual practices, or substance use. Exam revealed cervical lymphadenopathy and hepatosplenomegaly. Labs showed normal leukocyte count 8.4 thou/cmm with differential significant for reactive lymphocytosis 19% and bandemia 8%. Liver function tests were abnormal with elevated total bilirubin 3.8 mg/dL, AST 366 U/L, ALT 460 U/L, ALP 562 U/L. Synthetic function was intact. Hepatic ultrasound was unrevealing. Extensive infectious workup revealed acute EBV infection with serologies showing positive VCA IgM Ab 74.3 U/mL, negative VCA IgG Ab 11.9 U/mL, negative EA Ab < 5 U/mL, negative EBNA Ab < 3 U/mL. Patient was managed supportively with improved symptoms. She was instructed to avoid physical contact sports for one month upon discharge. Discussion: Clinically significant EBV induced hepatitis is a rare entity seen in < 5% of cases. Nevertheless, it is important to consider EBV as a causative pathogen of acute hepatitis. Heterophile antibody or Monospot test is the diagnostic test of choice with a sensitivity of 85% and a specificity of 100%;however, false negatives can occur especially early in the disease course. EBV serology has an improved sensitivity of 97% with a comparable specificity of 94%. As such, follow-up serology is necessary especially if clinical suspicion is high. While no specific EBV targeted therapies exist, it is important to identify it given the potential complications, including splenic rupture, airway obstruction, malignancies, lymphoproliferative disorders, among others.

S2703 A Rare Case of EBV Reactivation in an Immunocompetent Patient

Introduction: Hepatic involvement during an active primary Epstein-Barr virus (EBV) infection often results in mild, self-resolving elevation of transaminases and is associated with infectious mononucleosis (IM). EBV rarely reactivates, and most cases occur in immunocompromised individuals. We present a rare case of EBV reactivation in an immunocompetent patient only presenting with cholestatic liver injury. Case Description/Methods: A 19-year-old female with a history of resolved EBV IM one year prior presented with dark urine and jaundice. She had no fever, abdominal pain, nausea, vomiting, weight changes or night sweats. She had no history of illicit drug, tobacco or alcohol use, recent travel, or sick contacts. Her medications were loratadine and an OCP;she denied use of acetaminophen or herbal supplements. Family history was unrevealing. On exam she was jaundiced but otherwise normal. Initial laboratory tests showed AST 97 U/L, ALT 75 U/L, ALP 165 U/L, T-BILI 8.1 mg/dL, D-BILI 5.7 mg/dL. CT abdomen revealed splenomegaly. Work up revealed ASMA titer (1:40), but otherwise negative/ normal ANA, IgG, AMA, HCV Ab, HBV serologies, HAV IgM, CMV PCR, iron studies, tick borne serologies, SARS CoV-2 PCR, A1AT and ceruloplasmin. On the second day, the T-BILI peaked to 12.4 mg/dL, AST 151 U/L, ALT 131 U/L, ALP 237 U/L. (Fig.1) EBV serologies were positive (EBV VCA IgG >750.0 U/ml, EBV VCA IgM >160.0 U/ml), EBV viral load of 23,500 copy/ ml and negative monospot test. On day four, the LFTs improved and she was discharged. One month later LFTs had normalized, and she was asymptomatic. Discussion: EBV reactivation causing cholestatic liver injury is extremely rare in immunocompetent individuals. Furthermore, EBV-induced hepatitis is usually associated with IM but our patient's sole complaint was jaundice and dark urine. Interestingly, she had mononucleosis due to EBV one year prior with unremarkable LFTs. The fact that the hepatitis was caused by the reactivation of the virus instead of a primary infection may be the reason for lack of other symptoms. It is unclear whether EBV reactivation increases the risk of hepatitis. The diagnosis can be made without a liver biopsy if thorough work up for hepatitis is negative and the EBV serologies are positive. The disease is often self-limited and the use of antivirals is controversial and thus there is no clear indication. Our case demonstrates that EBV reactivation presenting without the 'classic' IM symptoms may be under-recognized as a cause of cholestatic liver injury. (Figure Presented).

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.

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System.

Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls.Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group.Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.