Barr Virus Infection Research Articles

Establishment of Epstein-Barr Virus (EBV) Latent Gene-Expressing T-Cell Lines with an Expression Vector Harboring EBV Nuclear Antigen 1.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is characterized by chronic or recurrent infectious mononucleosis-like symptoms and is associated with EBV-associated T/natural killer (NK)-cell lymphoproliferative disorders, which frequently lead to the development of life-threatening complications, such as virus-associated hemophagocytic syndrome and EBV-positive apparent leukemia/lymphoma mainly in T- and NK-cell lineages. In order to clarify the EBV genes responsible for the diseases, we introduced the plasmid coding sequences of EBV-encoded small RNAs (EBERs) and/or latent membrane protein (LMP) 1 into human T-lymphocyte virus-I-negative human T-cell lines using a gene expression vector harboring EBV nuclear antigen 1, established the G418-resistant transformants of five T-cell lines, and quantitatively examined the expression of EBERs and LMP1 using real-time reverse transcriptase-polymerase chain reaction. The expression levels of EBERs in T-cell transformants with EBER DNA paralleled those in EBV-positive human T- and NK-cell lines, SNTK cells. The expression of LMP1 mRNA varied in SNTK cells and in human T-cell transformants, and the expression of LMP1 mRNA in T-cell lines expressing both EBERs and LMP1 was much lower than that in the same cell line expressing LMP1 mRNA alone. The currently employed gene expression system and currently obtained transformants may be useful for the analyses of the pathophysiology of CAEBV and EBV-positive T/NK-cell lymphoproliferative disorders.

The Therapeutic Potential of Oxyhydrogen Gas in Oncology: A Study on Epstein–Barr Virus-Immortalised B-Lymphoblastoid (TK6) Cells

Cancer is a leading cause of mortality worldwide. B-cells are a keystone of the adaptive immune response and are essential for the presentation of tumor-associated antigens to various types of T-cells. Approximately 1.5% of global cancer cases, including breast and gastric carcinomas and both Hodgkin’s and non-Hodgkin’s lymphomas, are linked with prior Epstein–Barr Virus (EBV) infection. Such properties make EBV-infected lymphocytes ideal models for understanding the effect of oxyhydrogen gas on dysfunctional cell cycling. The aim of this study is to assess the effects of the direct infusion of oxyhydrogen gas on the replicative capacity of EBV-immortalised B-lymphocytes. Oxyhydrogen gas was directly infused into cell culture media. Cells were incubated in 95% air and 5% CO2 for up to 72 h. Cell enumeration was assessed with and without the addition of mitogenic growth stimuli, and subsequent cell-cycle analysis was performed. Cell enumeration: An initial trend of replicative inhibition of TK6 cells is noted with a single oxyhydrogen treatment at the 24 and 48 h time points. The daily addition of oxyhydrogen-infused media showed statistically relevant data at 24 and 48 h but not at 72 h. In mitogen-stimulated cells, a non-statistical trend of inhibition was observed at 24, 48 and 72 h. Analysis details a significant increase in DNA in the Sub G1 phase, indicating increased apoptosis.

Epstein–Barr virus (EBV) antibody changes over time in a general population cohort in rural Uganda, 1992–2008

BackgroundEpstein–Barr virus (EBV) infection is ubiquitous and in sub-Saharan Africa, occurs early in life. In a population-based rural African cohort, we leveraged historical samples from the General Population Cohort (GPC) in Uganda to examine the epidemiology of infection with EBV over time, in the era of HIV.MethodsWe used 9024 serum samples collected from the GPC in 1992, 2000, 2008, from 7576 participants across the age range (0–99 years of age) and tested for anti-EBV immunoglobulin G (IgG) antibodies to EAd, VCA, and EBNA-1 using a multiplex bead-based assay. The related gammaherpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV) seropositivity was also determined by detection of anti-KSHV IgG antibodies to K8.1 or ORF73 measured by recombinant protein enzyme-linked immunosorbent assay. Data on sex, age, and HIV serostatus were also collected. EBV seropositivity was modeled with age (excluding those under one year, who may have had maternal antibodies), sex, HIV serostatus, and KSHV serostatus using generalized linear mixed effects models to produce beta estimates.ResultsMore than 93% of children were EBV seropositive by one year of age. EBV seropositivity was significantly associated with KSHV seropositivity. Anti-EBNA-1 antibody levels decreased with increasing age and were lower on average in people living with HIV. In general, anti-EAd antibody levels increased with age, were higher in males and KSHV seropositive persons, but decreased over calendar time. Anti-VCA antibody levels increased with age and with calendar time and were higher in KSHV seropositive persons but lower in males.ConclusionsThis is the first study to identify factors associated with EBV antibodies across the entire life-course in rural sub-Saharan Africa. Consistent with other studies, EBV was near ubiquitous in the population by age one year. Patterns of antibodies show changes by age, sex and calendar time, but no association with HIV was evident, suggesting no relationship between EBV sero-epidemiology and the spread of HIV in the population over time in Uganda.

Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children

BackgroundChronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration.MethodsA retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated.ResultsThree patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment.ConclusionOur data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.

Nasopharyngeal carcinoma patient-derived xenograft mouse models reveal potential drugs targeting cell cycle, mTOR, and autophagy pathways

BackgroundNasopharyngeal carcinoma (NPC) is associated with Epstein–Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. MethodsBased on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. ResultsEverolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). ConclusionsHigh mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

Alice in wonderland syndrome – A medical enigma

Alice in Wonderland syndrome (AIWS) is a disorder in which patients report distorted visual perception and an impaired sense of time. It was first described in 1955 by the British psychiatrist John Todd, who associated these symptoms with disorders such as migraine and epilepsy. Before Todd’s observations, many symptoms of this disorder had made appearances in literature describing hysteria. Similar symptoms were observed in soldiers with occipital wounds after World Wars I and II. Patients with AIWS experience a plethora of symptoms such as, “kinetopsia” – Stationary objects appear to be moving, “total microsomatognosia” – Body parts appear unusually smaller. “Depersonalization” – Feeling of strangeness in perceiving one’s body image is common in AIWS. Often, this is accompanied by “derealisation” – Patients start perceiving their surroundings and the people around them as unreal. However, the patient is aware that this state of consciousness is not normal- which is what differentiates it from the state of psychosis. Other symptoms include: Dyschronometria, dysmorphops, macropsia, micropsia, kinetopsia, prosopometamorphopsia, and plagiopsia. In migraine patients, the prevalence rate of these symptoms increases to about 15%. Most symptoms of AIWS are ascribed to neurons of the central nervous system and cell columns that respond to specific sensory inputs (Ex- like visionary inputs of cortical areas V1–V5). Area V4 of the extrastriata visual cortex, particularly responds to the colors, whereas area V5 responds to movement. V4 and V5 also respond to shape and depth, but the bilateral loss of function of V4 results in achromatopsia (the inability to visualize color), and bilateral loss of V5 results in akinetopsia (the inability to visualize motion). Anatomically speaking, a critical region for developing this syndrome is the junction of three major areas, i.e., temporooccipital, parieto-occipital, and temporo-parietal junctions, known as the temporoparietal-occipital carrefour, point where our visual and somatosensory perceptions of the world are integrated to develop an external and internal representation of ourselves. AIWS remains a poorly understood and usually misdiagnosed syndrome. It is mostly associated with Epstein–Barr virus infection in children. Most cases of AIWS are expected to have a full remission of symptoms; sometimes, this may occur spontaneously with/without proper treatment. However, in cases with an associated chronic disease, like migraines and epilepsy, symptoms tend to occur in accordance with the active phases of these diseases. The number of fascinating disorders that surround and confound the medical community has no limit. The journey into the human brain is about as daunting and baffling as Alice’s journey into Wonderland. Efforts to understand the functioning and physiology of this extraordinary organ will keep both doctors and scientists on their toes for many years to come.

Safety Summary of Pediatric Inflammatory Bowel Disease Therapies

Therapeutic options for the treatment of pediatric inflammatory bowel disease include aminosalicylates, enteral nutrition , corticosteroids, immunomodulators , biologics, and emerging small molecule agents. Infectious risk due to systemic immunosuppression should be mitigated by appropriate screening before therapy initiation. Rare but serious malignancies have been associated with thiopurine use alone and in combination with anti-tumor necrosis factor agents, often in the setting of a primary Epstein–Barr virus infection. Potential agent-specific adverse events such as cytopenias , hepatotoxicity , and nephrotoxicity warrant regular clinical and laboratory monitoring.

Retrospective study of risk factors for pericardial effusion after haematopoietic stem cell transplantation in children

ABSTRACTObjectivesThe clinical characteristics, risk factors and survival prognosis of pericardial effusion (PE) after haematopoietic stem cell transplantation (HSCT) in children were investigated.MethodsClinical data of children who underwent HSCT at the Children's Hospital Affiliated with Chongqing Medical University from January 2016 to December 2022 were analysed retrospectively. Cox proportional hazards regression and the Kaplan-Meier method were used to analyse the risk factors for post-HSCT PE and its impact on outcomes, respectively.ResultsWe enrolled 452 patients with HSCT: 307 males and 145 females, with a median age of 3.4 (1.8 to 6.5) years at transplantation. Forty-five patients (10%) had PE within a median time of 25 (10.5 to 44) days, 42 (93%) within 100 days. Three patients with large PE were treated with pericardiocentesis and drainage, while the others were treated conservatively. Of the 45 patients with PE, 24 survived, and their PE disappeared after treatment. Graft-versus-host disease (GVHD) grade, abnormal pre-HSCT electrocardiogram, hepatic veno-occlusive disease (HVOD), pulmonary infection and Epstein–Barr virus (EBV) infection were risk factors for PE. The overall survival (OS) rates at 1, 3, and 5 years were 86.0%, 84.2%, and 82.3%, respectively. PE had a significant negative effect on OS after HSCT (P < 0.0001). Particularly, one patient with large PE died of pericardial tamponade.ConclusionsPost-HSCT PE usually occurred within 100 days. GVHD grade, abnormal pre-HSCT electrocardiogram, HVOD, pulmonary infection and EBV infection were closely related to PE. PE had a significant negative effect on OS rate.

A case of Epstein–Barr virus infection presenting with facial nerve palsy following the precursor condition of hemophagocytic lymphohistiocytosis

AbstractA 25‐year‐old man with infectious mononucleosis caused by Epstein–Barr virus infection developed facial nerve palsy. He was admitted to the hospital due to prolonged fever with liver enzyme elevations, diagnosed as primary Epstein–Barr virus infection. During conservative management, his fever and liver dysfunction persisted, with elevated serum inflammatory marker levels, and the precursor state of Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis was suspected. Although his symptoms and liver dysfunction trended toward amelioration after short‐term prednisolone, left‐sided facial palsy developed acutely. Facial palsy was considered Epstein–Barr virus infection‐related, and he recovered within 1 month following additional steroid therapy. Given the presence of the precursor condition of hemophagocytic lymphohistiocytosis just prior to facial palsy, hypercytokinemia was considered a possible pathogenic mechanism for the facial palsy. In patients with Epstein–Barr virus infection, facial palsy may occur independently of the recovery of other symptoms, and cytokine disturbance may affect its development.

Mortality risk in patients with anti-MDA5 dermatomyositis is related to rapidly progressive interstitial lung disease and anti-Ro52 antibody.

This study aimed to describe the clinical characteristics and analyze the poor prognostic factors in patients with anti-MDA5 dermatomyositis. A total of 126 adults with anti-MDA5 dermatomyositis were enrolled in this retrospective study. Information on survival time, cause of death, and baseline characteristics was collected. Patients were divided into two groups: a survival group and a non-survival group. Items with clinical significance that showed significant differences between the two groups were screened by Kaplan-Meier and Cox regression analyses to identify the predictors of poor survival. Thirty-two patients were included in the non-survival group, most of whom died from respiratory failure, with pulmonary infection accounting for half. Epstein-Barr virus infection was relatively common in both groups. Aspartate transaminase, lactate dehydrogenase, and ferritin levels; erythrocyte sedimentation rate; and anti-Ro52 antibody levels were significantly higher, while the lymphocyte count was lower in the non-survival group compared with the survival group. Notably, patients in the non-survival group were more likely to present with rapidly progressive interstitial lung disease than those in the survival group. Kaplan-Meier and Cox multivariate regression analyses revealed that the prevalence of rapidly progressive interstitial lung disease, levels of anti-Ro52 antibody, and age > 57 years were important prognostic factors independent of multiple clinical parameters. Rapidly progressive interstitial lung disease, anti-Ro52 antibody levels, and age > 57 years are possible predictors of mortality risk in patients with anti-MDA5 dermatomyositis.

LMP1 Encoded By Epstein–Barr Virus May Activate Ahr Through the ERK Pathway in Nasopharyngeal Carcinoma Cells

Aim: To investigate the role of AHR in nasopharyngeal carcinoma (NPC) and explore the relationship between Epstein–Barr virus (EBV) infection and the AHR pathway. Methods: The effect of LMP1 on the expression of AHR was analyzed using real-time PCR and western blot. Proliferation and migration of cells were assessed using CCK8 and Transwell analysis. Results: EBV infection downregulated the expression of AHR in NPC cells, possibly through activation of the ERK pathway by LMP1 thereby accelerating AHR proteasomal degradation following translocation to the nucleus. Cell proliferation, migration and autophagy are promoted by activating the AHR pathway. Conclusion: In NPC cells, LMP1 increases the phosphorylation of ERK, which may activate the AHR pathway.

BI19 Cutaneous post-transplant lymphoproliferative disorder in an immunosuppressed patient

Abstract Post-transplant lymphoproliferative disorders (PTLDs) are a common form of de novo neoplasia developing in patients with immunosuppression following a transplant. The majority are associated with Epstein–Barr virus (EBV) infection. Cutaneous PTLD manifestations are rare and not well documented in literature. We present a case of systemic PTLD with secondary extensive cutaneous involvement 4 months after allogenic stem cell transplant for JAK2-mutated myelofibrosis. A 68-year-old man was admitted to the haematology department with fevers, diarrhoea, cytopenia, EBV viraemia and a nodular rash behind his ears. Biopsies from colonoscopy confirmed monomorphic PTLD with subsequent extensive ileocalceal lymphadenopathy area detected on computed tomography. Asymptomatic, large, hardened violaceous nodules on the head and neck worsened further. Skin biopsy showed an infiltrate of atypical lymphocytes in the dermis, composed predominantly of large lymphoid cells with visible prominent nucleoli. A limited immunohistochemical panel showed positivity for BCL-2 but not CD20. EBV-encoded RNA in situ hybridization was also positive. Features were compatible with cutaneous involvement by the known monomorphic PTLD. Unfortunately, the patient deteriorated with haemodynamic instability due to sepsis, despite two further infusions of rituximab, and was directed to the palliative team. He died soon after the discontinuation of all treatments. PTLD has a wide spectrum of clinical manifestations. It is classified into three nondestructive types: polymorphic, monomorphic and classic Hodgkin lymphoma type. It can have a poor prognosis so it should always be considered as a diagnosis in transplant patients. Monomorphic PTLDs tend to be more aggressive and rarely respond to immunosuppression reduction. On the contrary, primary cutaneous involvement is rare and seems to have a favourable outcome. Treatment depends on the severity of the disease, and both localized and systemic therapies have been used. Transplant patients should have long-term follow-up to diagnose and promptly treat possible complications.

Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer.

Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/β-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.

Detection of Epstein–Barr virus infection in thymic epithelial tumors by nested PCR and Epstein–Barr-encoded RNA ISH

BackgroundEpstein–Barr virus (EBV) is well known to be associated with a lot of tumors, including lymphoma, nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and some other carcinomas with similar lymphoepithelioma-like features. However, the association between EBV and thymic epithelial tumors (TETs) is inconclusive as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. The geographical difference of the patients is also one of the reasons for the different points of view.MethodsIn our study, we examined 72 thymomas, including 3 cases of type A thymomas, 27 cases of type AB, 6 cases of type B1, 26 cases of type B2 and 10 cases of type B3 thymomas, and 15 thymic carcinomas to detect the viral genome at both DNA and RNA levels. The genome DNA of fresh tissues was first screened by nested polymerase chain reaction (PCR), which could be regarded as the most sensitive method to detect small amounts of DNA. Then all the tissue blocks were further submitted for viral localization by Epstein–Barr-encoded RNA (EBER) ISH. Group parameters were assessed using the chi-square test at a significance level of p < 0.05.ResultsNested PCR results showed that none of type A, eight (29.6%) type AB, one (16.7%) type B1, fifteen (57.7%) type B2, and four (40.0%) type B3 were positive for EBV genome. However, none of them detected EBER expression except for one case of type B2 thymoma. Fourteen (93.3%) thymic carcinomas were positive for EBV by nested PCR, of which three displayed weak nuclear signals within the tumor cells by EBER ISH.ConclusionsThese results showed that nested PCR was a sensitive method for screening the EBV genome in thymic epithelial tumors. As the malignancy of thymoma increases, the rate of EBV infection became higher. Thymic carcinomas were well associated with the Epstein–Barr virus.There was significant association between the EBV infection rate and thymoma type (p < 0.05). We further analyzed the association between EBV infection and myasthenia gravis. However, it showed no significant difference(p = 0.2754), although the EBV infection rate was higher in the thymomas with myasthenia gravis.

Association Between Human Epstein–Barr Virus and Brain Cancer: A Systematic Review and Meta-Analysis

Aim: The aim of this study was to investigate the pooled prevalence and potential correlation between Epstein–Barr virus (EBV) infection and brain cancers. Materials &amp; methods: We searched for relevant studies in main databases and analyzed the heterogeneity, odds ratio and corresponding 95% CI among all studies using STATA software V.14. Results: Fourteen articles were included in the meta-analysis. The pooled prevalence of EBV among brain cancer patients was 9% (95% CI: 3–16%; I2 = 91.06%). An association was found between EBV and brain cancer (OR: 6.90 [95% CI: 1.81–26.28]; I2 = 0%]). Conclusion: The results of this study indicate a significant association between EBV infection and brain cancer, suggesting EBV infection is a potential risk factor for brain cancer development.

MAGT1 deficiency in XMEN disease is associated with severe platelet dysfunction and impaired platelet glycoprotein N-glycosylation

BackgroundX-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia (XMEN) disease is a primary immunodeficiency due to loss-of-function mutations in the gene encoding for magnesium transporter 1 (MAGT1). Furthermore, as MAGT1 is involved in the N-glycosylation process, XMEN disease is classified as a congenital disorder of glycosylation. Although XMEN-associated immunodeficiency is well described, the mechanisms underlying platelet dysfunction and those responsible for life-threatening bleeding events have never been investigated. ObjectivesTo assess platelet functions in patients with XMEN disease. MethodsTwo unrelated young boys, including one before and after hematopoietic stem cell transplantation, were investigated for their platelet functions, glycoprotein expression, and serum and platelet-derived N-glycans. ResultsPlatelet analysis highlighted abnormal elongated cells and unusual barbell-shaped proplatelets. Platelet aggregation, integrin αIIbβ3 activation, calcium mobilization, and protein kinase C activity were impaired between both patients. Strikingly, platelet responses to protease-activated receptor 1 activating peptide were absent at both low and high concentrations. These defects were also associated with decreased molecular weights of glycoprotein Ibα, glycoprotein VI, and integrin αIIb due to partial impairment of N-glycosylation. All these defects were corrected after hematopoietic stem cell transplantation. ConclusionOur results highlight prominent platelet dysfunction related to MAGT1 deficiency and defective N-glycosylation in several platelet proteins that could explain the hemorrhages reported in patients with XMEN disease.

Human cytomegalovirus and Epstein-Barr virus infections occurring early after transplantation are risk factors for antibody-mediated rejection in heart transplant recipients.

Antibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR. This study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1-90 days after transplantation) were considered. Fisher's exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection. We observed a positive statistical association between CMV and EBV infections (two-sided Fisher's exact test, p = 0.0136) and between EBV infection and AMR (two-sided Fisher's exact test, p = 0.0034). Logistic regression analysis revealed a direct statistical association between CMV and EBV infections and AMR risk (p = 0.037 and 0.006 and odds ratio = 1.72 and 2.19, respectively). AMR occurrence was associated with increased viral loads of both CMV and EBV early after transplantation. These findings suggest the role of CMV and EBV infections as relevant risk factors for AMR in HTxs for the first time.

Helicobacter pylori and Epstein-Barr Virus Co-Infection in Gastric Disease: What Is the Correlation with p53 Mutation, Genes Methylation and Microsatellite Instability in a Cohort of Sicilian Population?

Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23%, p = 0.0456). Finally, for p53 mutation in the EBV group, exon 6 was, significantly, most frequent in comparison to others (p = 0.0124), and in the Hp-EBV group exon 8 was, significantly, most frequent in comparison to others (p < 0.0001). A significant positive relationship was found between patients with infection (Hp, EBV or both) and p53 mutation (rho = 0.383, p = 0.0001), methylation status (rho = 0.432, p < 0.0001) and microsatellite instability (rho = 0.285, p = 0.004). Finally, we observed among infection and methylation status, microsatellite instability, and p53 mutation a significant positive relationship only between infection and methylation status (OR = 3.78, p = 0.0075) and infection and p53 mutation (OR = 6.21, p = 0.0082). According to our analysis, gastric disease in the Sicilian population has different pathways depending on the presence of various factors, including infectious agents such as Hp and EBV and genetic factors of the subject.

Unusual Presentation of Brain Tumor in a Child: A Case Report

The most popular type of neurological tumor in childhood is medulloblastoma, which is the most malignant neoplasm of the posterior fossa and cerebellum. Central nervous system neoplasms can cause symptoms and signs due to local invasion, compression of normal structures, and increased intracranial pressure by either a mass effect or obstruction of cerebrospinal fluid flow, resulting in hydrocephalus. Usually, headache is the most common symptom of central nervous system tumors, and the median duration between symptoms beginning and diagnosis of brain tumors in children ranges from 2.5 to 3.5 months. Furthermore, several predisposing factors for brain tumors have been identified such as Epstein–Barr virus infection, exposure to ionizing radiation, and inherited diseases. Recently, the advances in diagnosis and treatment have improved the survival of many children with neurological neoplasms. However, this therapy is associated with long-term complications, and its prognosis remains poor. We present the case of a 4-year-old girl with adequate neuropsychomotor development who presented to the pediatric emergency center with a 14-day history of headache, which was prominent in the morning, neck, back, and bilateral leg pain two days prior to presentation. Brain and Spine Magnetic resonance imaging revealed a cerebellar mass lesion in the posterior fossa. The patient underwent surgery, followed by histopathological and immunohistochemical staining. This case is considered rare and distinctive because the symptoms included only headache for two weeks, no impaired vision, no vomiting, no mental disorders, no abnormal gait, and no ataxia or body imbalance. We report this case to focus on the features of the manifestation and hence increase the chances of timely diagnosis in the future. Consequently, the probability of central nervous system tumors should always be considered in children with headache, and they must be under regular follow-up for early diagnosis and treatment.

Concordance of adenosine deaminase with immunoglobulins and lymphocyte subsets in EBV-related diseases

BackgroundClinical manifestations of Epstein–Barr virus (EBV) infection are diverse. This study aimed to explore the immune response in EBV-related diseases and the correlation between immune cells and adenosine deaminase (ADA) levels.MethodsThis study was conducted at the Children’s Hospital of Soochow University. In total, 104 patients with EBV-associated respiratory tract infection (EBV-RTI), 32 patients with atypical EBV infection, 54 patients with EBV-associated infectious mononucleosis (IM1, with normal alanine aminotransferase [ALT] levels), 50 patients with EBV-IM2 (with elevated ALT levels), 50 patients with acute respiratory infection (AURI, with other pathogens), and 30 healthy controls were enrolled in this study. Indicators of ADA, immunoglobulins (Igs), and lymphocyte subsets were analyzed for EBV-related diseases.ResultsDifferences in the white blood cell, lymphocyte counts, ADA levels, IgA, IgG and IgM titers, percentage of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD3−CD19+, and CD19+CD23+ lymphocytes, and CD4+/CD8+ ratio between EBV-related disease groups were all statistically significant (P < 0.01). ADA levels in the EBV-related disease groups were significantly higher than those in the control group (P < 0.01). The lymphocyte count, ADA levels, IgA and IgG titers, and percentage of CD3+ and CD3+CD8 + lymphocytes in the atypical EBV infection, EBV-IM1, and EBV-IM2 groups were significantly higher than those in the EBV-RTI, AUTI, and control groups (P < 0.01), whereas the percentage of CD3+CD4+, CD3−CD19+, and CD19+CD23+ lymphocytes and CD4+/CD8+ ratio showed the opposite trend. ADA levels were consistent with and closely related to the viral load and cellular and humoral immunity in EBV-related diseases.ConclusionsADA levels, humoral immunity, and cellular immunity were diverse in EBV-related diseases, and ADA was closely related to Igs and lymphocyte subsets.