Barr Virus Infection Research Articles

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder.

PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein-Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy.

The Association between Infectious Mononucleosis and Cancer: A Cohort Study of 24,190 Outpatients in Germany.

Background: Cancer represents one of the leading causes of death worldwide. Besides genetic risk factors and non-communicable diseases, chronic infections including Epstein−Barr virus (EBV) infection have been identified as promotors of cancer. In the present manuscript, we evaluated the association between infectious mononucleosis, the clinical manifestation of EBV infection, and cancer development in a real-word cohort of outpatients in Germany. Methods: We used the Disease Analyzer database (IQVIA) and matched a total of 12,095 patients with infectious mononucleosis to a cohort of individuals without infectious mononucleosis based on age, sex, index year, and annual patient consultation frequency between 2000 and 2018. Results: Patients diagnosed with infectious mononucleosis had a cancer incidence of 5.3 cases per 1000 person years versus 4.4 cases per 1000 person years for patients without infectious mononucleosis. In multivariable regression models, infectious mononucleosis showed a trend towards a higher incidence of cancer in general in the age group > 50 years (incidence rate ratio (IRR): 1.32; 95% CI: 1.04−1.67) and among men (IRR: 1.36; 95% CI: 1.07−1.72). Infectious mononucleosis was significantly associated with an increased incidence of tumors of the hematopoietic and lymphoid tissues (IRR: 1.75; 95% CI: 1.22−2.50) and showed a strong trend towards an association with prostate cancer (IRR: 3.09; 95% CI: 1.23−7.76). Conclusion: Infectious mononucleosis is associated with an increased incidence of certain cancer types. The present data from a large real-world cohort support the evidence on a role of EBV in the development of different malignancies and could trigger research efforts to further elucidate its precise involvement in the carcinogenic process.

Identification of key genes and biological pathways in different parts of yak oviduct based on transcriptome analysis.

The oviduct consists of three parts: the infundibulum (In), ampulla (Am), and isthmus (Is). These have the same histological structure, but different physiological functions. In this study, transcriptomics was used to analyze mRNA in these three parts of yak oviduct. The results showed that there were 325 up-regulated genes and 282 down-regulated genes in the infundibulum and ampulla. Moreover, there were 234 up-regulated genes and 776 down-regulated genes in the isthmus and ampulla, as well as 873 up-regulated genes and 297 down-regulated genes in the infundibulum and isthmus. The expression of C3 in the infundibulum was significantly higher than that in the ampulla and isthmus. The expression of FAU in the isthmus was significantly lower than that in the ampulla and infundibulum, and the expression of EEF1A1 in the ampulla was significantly higher than that in the ampulla and infundibulum. When the infundibulum was compared with the ampulla and isthmus, it was found that the up-regulated genes were enriched in the lysosome, phagosome, staphylococcus aureus infection, and leishmaniasis pathway. When the isthmus was compared with the ampulla and infundibulum, the up-regulated genes were present in the apoptosis pathway, oxidative phosphorylation, and viral myocarditis pathway. When the isthmus was compared with the infundibulum and ampulla, the down-regulated pathways were protein processing in the endoplasmic reticulum and the endocytosis. The Epstein-Barr virus infection pathway was up-regulated according to a comparison of the isthmus and infundibulum and was down-regulated based on a comparison of the isthmus and ampulla. Transcriptional misregulation in the Middle East pathway was up-regulated based on a comparison of the isthmus and ampulla and was down-regulated based on a comparison of the isthmus and infundibulum. ERBB2, JUP, CTNND1, and KRT7 were defined as the hub genes of the yak oviduct. The results of this study provide sufficient omics data for yak fertilization, which is also of great significance to altitude medicine.

Epstein–Barr virus-related dacryocystitis: a case report

Background and objectiveAcute dacryocystitis is an atypical and rare manifestation of pediatric mononucleosis still widely underdiagnosed in clinical practice. We report this rare condition and describe challenges in its diagnosis and treatment on the basis of a presented case.Case presentationA 6-year-old Caucasian girl without any ophthalmic history was admitted for right preseptal cellulitis requiring intravenous antibiotic therapy. During hospitalization, she developed a fluctuating lump in the nasolacrimal region which resembled an abscess, both clinically and radiologically. There was no spontaneous purulent discharge. Serology was positive for acute mononucleosis and Epstein–Barr virus-related dacryocystitis was diagnosed. Following multidisciplinary discussion, she was treated conservatively with digital lacrimal sac massages and intravenous antibiotic therapy with an excellent outcome.DiscussionThis rare form of Epstein–Barr virus is poorly documented in the literature, and thus barely known. As initial symptoms are nonspecific (rhinitis, fever, eyelid edema and erythema lack of purulent discharge, and moderate bilateral cervical lymphadenopathy), diagnosis is often difficult. Nevertheless, differentiating between dacryocystitis and abscess is crucial to select the appropriate treatment and avoid unnecessary, potentially harmful surgery. Conservative management of dacryocystitis appears to be the gold standard of treatment.ConclusionAcute dacryocystitis in children free of ophthalmic history should raise suspicion of primary Epstein–Barr virus infection. With conservative treatment, prognosis appears to be excellent; therefore, surgery should be avoided as much as possible.

Epstein-Barr viral infection is a global epidemiological problem

The number of studies devoted to Epstein-Barr viral infection (EBV infection) has been growing in recent years. However, they all relate to the clinical aspects of this problem. Epidemiology issues remain practically unexplored. A review of domestic and foreign publications has shown that at the present stage there is a high intensity of the epidemic process of EBV infection both in Russia and abroad. The main indicators of unfavorable epidemiological situation are the ubiquitous spread of the pathogen and the increase in the incidence of infectious mononucleosis in recent years. The deterioration of the epidemic situation of EBV infection is influenced by changes in the immunological reactivity of various population groups due to the spread of HIV, HBV, HCV, the causative agent of tuberculosis and SARS-CoV-2. The above makes it possible to classify the problem as a global one and determines the need for the rapid implementation of the system of epidemiological surveillance of EBV infection and optimization of the complex of preventive and anti-epidemic measures. Reducing the burden of EBV is possible only with the consolidated participation of specialists of various profiles.

Epstein-Barr Virus-Induced Genes and Endogenous Retroviruses in Immortalized B Cells from Patients with Multiple Sclerosis.

The immune pathogenesis of multiple sclerosis (MS) is thought to be triggered by environmental factors in individuals with an unfavorable genetic predisposition. Epstein-Barr virus (EBV) infection is a major risk factor for subsequent development of MS. Human endogenous retroviruses (HERVs) can be activated by EBV, and might be a missing link between an initial EBV infection and the later onset of MS. In this study, we investigated differential gene expression patterns in EBV-immortalized lymphoblastoid B cell lines (LCL) from MS-affected individuals (MSLCL) and controls by using RNAseq and qRT-PCR. RNAseq data from LCL mapped to the human genome and a virtual virus metagenome were used to identify possible biomarkers for MS or disease-relevant risk factors, e.g., the relapse rate. We observed that lytic EBNA-1 transcripts seemed to be negatively correlated with age leading to an increased expression in LCL from younger PBMC donors. Further, HERV-K (HML-2) GAG was increased upon EBV-triggered immortalization. Besides the well-known transactivation of HERV-K18, our results suggest that another six HERV loci are up-regulated upon stimulation with EBV. We identified differentially expressed genes in MSLCL, e.g., several HERV-K loci, ERVMER61-1 and ERV3-1, as well as genes associated with relapses. In summary, EBV induces genes and HERV in LCL that might be suitable as biomarkers for MS or the relapse risk.

Epstein-Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells.

Epstein-Barr virus or human herpesvirus 4 (EBV/HHV-4) is an omnipresent oncovirus etiologically associated with various B-cell lymphomas and epithelial cancers. The malignant transformation associated with the persistent expression of viral proteins often deregulates the host cellular machinery and EBV infection is coupled to elevated levels of reactive oxygen species. Here, we investigated the role that the glutamate transporter EAAT3 plays in regulating the antioxidant system as a protective mechanism of EBV-infected cells against the virus-induced oxidative stress. Our study demonstrated that the expression of EAAT3 was upregulated and localized to the plasma membrane in EBV latently infected and de novo EBV-infected cells. EAAT3 was regulated by the transcription factor NFAT5 in the infected cells. Membrane localized EAAT3 was found to be involved in the transportation of glutamate from the extracellular space into the cell, as EAAT3 and NFAT5 inhibitors markedly reduced the levels of intracellular glutamate levels in EBV latently infected cells. Additionally, our data demonstrated a notable decrease in the intracellular glutathione levels following treatment with an EAAT3 inhibitor. Collectively, our results suggest that upregulation of the glutamate transporter EAAT3 is an adaptation of EBV-infected cells to maintain cellular redox homeostasis against the virus-induced oxidative stress, and that this cellular balance could be therapeutically destroyed by targeting EAAT3 to impede EBV-associated cancers.

Analysis of exosomal competing endogenous RNA network response to paclitaxel treatment reveals key genes in advanced gastric cancer

Exosome is an important component of the tumor immune microenvironment and plays critical role in cancer pathogenesis. The exosome transcriptome of gastric cancer (GC) response to paclitaxel chemotherapy has not been investigated in the past. ceRNA microarrays were performed in exosomes from six advanced GC patients before and after paclitaxel treatment. Bioinformatics tools were used to identify differential expressing genes and construct competing endogenous RNA (ceRNA) networks. The importance of hub genes in the ceRNA network was confirmed by survival analysis and functional analysis. A total of 213 differential mRNAs, 370 lncRNAs, and 376 circRNAs were identified, and hub genes in ceRNA networks were screened. The differential genes were associated with GO terms SNAP complex, gap junction, protein transporter activity, cytokine receptor, and KEGG pathways synaptic vesicle cycle, propanoate metabolism, Epstein-Barr virus infection, heparin, and steroid biosynthesis, and beta-alanine metabolism. ULK2, CYP2R1, BTLA, and miR-105-5p are prognostic genes for overall survival. Paclitaxel may target ULK2 which is involved in mitosis and cell cycle. miR-105-5p may target ULK2 3'UTR. The work for the first time identified exosomal RNA biomarkers and constructed a ceRNA network in GC response to paclitaxel, revealed novel molecular mechanisms of GC, and provided new candidates for GC diagnosis and treatment.

Relationship between Iron deposition and T lymphocytes in children with β-thalassemia with haematopoietic stem cell transplantation.

β-Thalassemia cellular immunity is associated with iron overload. However, the relationship between varying degrees of iron deposition and T cell immune recovery after allogeneic haematopoietic stem cell transplantation(allo-HSCT) in children remain unclear. A retrospective analysis was performed on 84 children with β-Thalassemia undergoing sibling allo-HSCT. According to the degrees of hepatic iron deposition, patients were divided into four classes. T lymphocyte counts were measured. Hepatic iron deposition was assessed by T2* MRI. Epstein-Barr virus and cytomegalovirus infection rates and graft-vs.-host disease incidence were recorded. Immune recovery after allo-HSCT was compared between the two groups. Normal vs. mild group: CD4 cells were higher at 1, 3, and 6 months (P < 0.05), CD3 and CD8 cells were higher at 3 and 6 months, and 1 year in normal group (P < 0.05). Normal vs. moderate group: CD3 and CD4 cells were higher at 1, 3 and 6 months, and 1 year (P < 0.05), CD8 cells were higher at 1 and 3 months, and 1 year in normal group (P < 0.05). Normal vs. severe group: CD3, CD4 and CD8 cell at 1, 3 and 6 months, and 1 year in normal group (P < 0.05). Mild vs. moderate group: CD3, CD4 and CD8 cells were higher at 1 month in mild group (P < 0.05). Mild vs. severe group: CD4 cells were higher at 1, 3 and 6 month, and 1 year (P < 0.05), CD3 and CD8 cells were higher at 1 month in mild group (P < 0.05). Moderate vs. severe group: CD4 cells were higher at 3 months (P < 0.05), CD8 cells were higher at 6 months in moderate group (P < 0.05). The hepatic T2* values were positively correlated with CD3, CD4 and CD8 cells. The infection rates of Epstein-Barr virus and cytomegalovirus were significantly different among the groups (P < 0.05). Iron deposition affects immune recovery of T lymphocytes after allo-HSCT in children with β-thalassemia. The lower the levels of iron deposition, the greater the CD4 cell count.

Circulating Epstein-Barr virus DNA associated with hepatic impairment and its diagnostic and prognostic role in patients with gastric cancer.

Epstein–Barr virus (EBV) infection may affect all tissues and organs of the body. Little is known about the impact of this entity on its systematic incorporation in patients with gastric cancer (GC). This study enrolled a total of 113 GC patients with EBV infection (EBVaGC) and 167 GC patients without EBV infection (EBVnGC). It was found that the CRP levels (indicative of inflammatory status) were significantly increased in EBVaGC compared with those in EBVnGC (12.11 mg/L vs. 5.72 mg/L, P = 0.008), but WBC and neutrophils counts were similar in both groups (P > 0.05). Consistent elevations in the levels of liver enzymes, ALP and GGT, with incompatible alterations in ALT or AST were observed in EBVaGC. Slightly prolonged coagulation indices, PT and INR, and decreased albumin consistently suggested impaired synthesis capability of the liver in EBVaGC (all P < 0.05). The level of circulating EBV DNA was positively correlated with the level of GGT, tumor marker CA72-4 and the lymphocyte infiltration in tumor tissues (all P < 0.05). Of note, the EBV associated high-lymphocyte infiltrated tissues presented rich CD8 + T cells. Circulating EBV DNA further showed a predictive role in distinguishing EBVaGC from EBVnGC (AUC 0.79, 95% CI 0.73 to 0.85, P < 0.001), and was associated closely with better overall survival (HR 0.45, 95% CI 0.21 to 0.96, P = 0.039). EBV infection in patients with gastric cancer may be linked to hepatic impairment and immune response. Circulating cell-free EBV DNA is not only a biomarker for the screening of an EBV-related GC subtype but is also an independently prognosis factor for the long-term survival benefit in GC patients.

The Importance of Toll-like Receptor 9 Expression on Monocytes and Dendritic Cells in the Context of Epstein-Barr Virus Infection in the Immunopathogenesis of Primary Glomerulonephritis.

Toll-like receptor 9 (TLR9) is activated by unmethylated cytosine-phosphate-guanosine (CpG) dinucleotides found in the genomes of pathogens such as Epstein–Barr virus (EBV). The aim of this study was to determine the role of TLR9 in the immunopathogenesis of IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) in the context of Epstein–Barr virus (EBV) infection. For this purpose, the frequency of TLR9-positive monocytes and dendritic cells (DCs, i.e., BDCA-1; myeloid dendritic cells, and BDCA-2; plasmocytoid dendritic cells) was studied, and a quantitative analysis of the concentration of TLR9 in the serum of patients diagnosed with IgAN and MPGN was undertaken. Higher frequencies of TLR9-positive DCs and monocytes in IgAN and MPGN patients were observed as compared with the control group. Patients diagnosed with GN exhibited a higher percentage of BDCA-1+CD19− and BDCA-2+CD123+ DCs than patients in the control group. Moreover, serum TLR9 concentration was shown to be significantly correlated with EBV DNA copy number/µg DNA, IgG, IgM, serum albumin, total protein in 24-h urine collection test and the frequency of BDCA-2+CD123+ DCs in peripheral blood. Our findings confirm that TLR9 may be involved in the development of IgAN and MPGN.

What? Is Epstein–Barr Virus Infection Linked to Multiple Sclerosis?

What? Is Epstein–Barr Virus Infection Linked to Multiple Sclerosis?

Analysis of Epstein-Barr Virus (EBV) and PD-L1 Expression in Nasopharyngeal Carcinoma Patients in a Non-Endemic Region.

Background: The purpose of this study was to evaluate the status of Epstein–Barr virus (EBV) infection and the expression of programmed cell death ligand-1 (PD-L1) in tumor samples from patients with nasopharyngeal carcinoma (NPC). Methods: Evaluation of EBV infection was performed through the detection of EBV-encoded small ribonucleic acids (EBER) by in situ hybridization, and PD-L1 expression was performed through immunohistochemistry. Results: In total, 124 samples were evaluated for EBER and 120 for PD-L1 expression. A total of 86.3% of cases were positive for EBER and 55.8% were positive for PD-L1. There was a correlation between EBER positivity and the presence of undifferentiated carcinoma histology (p = 0.007) as well as the absence of tobacco history (p = 0.019). There was a correlation between PD-L1 expression and EBER positivity (p = 0.004). There was no statistically significant difference between overall survival (OS) and EBER (p = 0.290) or PD-L1 (p = 0.801) expression. Conclusions: This study corresponds to one of the largest cohorts of NPC in a non-endemic region. Phase III studies with checkpoint inhibitors are ongoing and may provide more data about the role of PD-L1 expression in this disease.

The role of highly toxigenic CagA and VacA strains of Helicobacter pylori in gastric carcinogenesis. Review

Gastric cancer takes the 4th place as the main cause of death among oncological diseases in the world. The risk factors of gastric cancer include genetic predisposition, alcohol abuse, smoking, low socio‑economic level, nutritional characteristics, Epstein–Barr virus and Helicobacter pylori infection. Helicobacter pylori bacterium is the only statistically proven risk factor for stomach cancer. Gastric cancer develops in less than 3 % of ­H. pylori ‑infected patients, suggesting a unique interaction between the host immune response and H. pylori virulence factors. Expression of oncogenic cytotoxin‑associated protein gene A (CagA), vacuolating cytotoxin A (VacA), and outer membrane proteins is important for H. pylori in host pathogenesis. The paper gives consideration for the relationship between the virulence factors of H. pylori and the host, which is necessary for a better understanding of the pathogenesis and prevention of carcinogenesis. The strategy for the prevention of gastric cancer includes eradication therapy, but it is complicated by the growth of resistance to antimicrobial drugs. Only insignificant number of papers investigate effects of pathogenicity factors of H. pylori (CagA+ and VacA+) on the development of atrophy, intestinal metaplasia and dysplasia. In the literature, there is little data on the difference in antibiotic resistance between H. pylori highly toxigenic and non‑toxigenic strains. The aim of the article is to present current data on the impact of highly toxigenic CagA+VacA+ strains of H. pylori on the processes of gastric carcinogenesis and to determine their role in resistance to clarithromycin. Investigation of the relationship between highly toxigenic CagA and VacA strains with clinical and morphological manifestations of gastritis and antibiotic resistance will enable preventing the progression of precancerous changes and using effective treatment tactics.

Identification of hub genes associated with acute kidney injury induced by renal ischemia-reperfusion injury in mice.

Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia–reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia–reperfusion injury (IRI-AKI). Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)–hub gene and miRNA–hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Result: A total of 323 common differentially expressed genes were identified in the renal ischemia–reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein–Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes. Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia–reperfusion injury–acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia–reperfusion injury–acute kidney injury.

Cholestatic Hepatitis Secondary to Epstein–Barr Virus Infection in Children: Case Series and Review of the Literature

Abstract Objective Cholestatic hepatitis (CH) secondary to Epstein–Barr virus (EBV) infection is a rare clinical condition in children and adolescents, which was reported in 5% of patients. Herein, we aimed to present our pediatric cases of EBV-induced CH with a comprehensive review of previously reported patients. Methods Three cases of EBV-induced CH diagnosed in our department were included in the study. EBV diagnosis was established with positive viral capsid antigen immunoglobulin M and immunoglobulin G. A search of English literature on pediatric cases with EBV-induced CH was conducted on common search engines (PubMed and GoogleScholar). Results We report three novel cases (aged 6, 15, and 16 years) presented with infectious mononucleosis and jaundice. The physical examination revealed mild hepatomegaly in all of them. In our cases, a total of 21 pediatric patients with EBV-induced CH were reported until now (52.4% male), with a median age of 15 (1–18) years. Regarding all patients, the most common symptoms were fever (94.1%) and jaundice (84.6%). In laboratory results, aspartate aminotransferase [308 (62–2,148) IU/L], alanine aminotransferase [312 (79–899) IU/L], and γ-glutamyl transpeptidase [328.9 ± 198.6 IU/L] levels were elevated. Hyperbilirubinaemia was observed in all cases with a median direct bilirubin level of 3.9 (1.9–21.8) mg/dL. A thickened gallbladder wall was the most common (50%) finding in the abdominal ultrasonography of the cases. Most of the reported patients recovered under supportive treatment without any further morbidity. Conclusions Although EBV-induced CH is an atypical presentation for children, it should be considered in the differential diagnosis of cholestasis. Supportive therapies are the mainstay of treatment in most of these cases.

A computed tomography-based preoperative risk scoring system to distinguish lymphoepithelioma-like gastric carcinoma from non-lymphoepithelioma-like gastric carcinoma.

PurposeThe aim of this study was to develop a preoperative risk scoring model for distinguishing lymphoepithelioma-like gastric carcinoma (LELGC) from non-LELGC based on contrast-enhanced computed tomography (CT) images.MethodsClinicopathological features and CT findings of patients with LELGC and non-LELGC in our hospital from January 2016 to July 2022 were retrospectively analyzed and compared. A preoperative risk stratification model and a risk scoring system were developed using logistic regression.ResultsTwenty patients with LELGC and 40 patients with non-LELGC were included in the training cohort. Significant differences were observed in Epstein–Barr virus (EBV) infection and vascular invasion between the two groups (p < 0.05). Significant differences were observed in the distribution of location, enhancement pattern, homogeneous enhancement, CT-defined lymph node status, and attenuations in the non-contrast, arterial, and venous phases (all p < 0.05). Enhancement pattern, CT-defined lymph node status, and attenuation in venous phase were independent predictors of LELGC. The optimal cutoff score of distinguishing LELGC from non-LELGC was 3.5. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the training cohort were 0.904, 87.5%, 80.0%, and 85.0%, respectively. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the validation cohort were 0.705 (95% CI 0.434–0.957), 75.0%, 63.6%, and 66.7%, respectively.ConclusionA preoperative risk identification model based on CT imaging data could be helpful for distinguishing LELGC from non-LELGC.

A retrospective analysis of EBV-DNA status with the prognosis of lymphoma.

Epstein–Barr virus (EBV) infection is proved to be associated with clinicopathology of lymphoma. However, little is known about the relationship between EBV‐DNA status after treatment and prognosis. In this study, real‐time polymerase chain reaction (PCR) was used for quantitative detection of EBV‐DNA load in peripheral blood of all 26,527 patients with lymphoma, and the clinical characteristics and prognosis of 202 patients were retrospectively analysed, including 100 patients with positive EBV‐DNA and 102 randomly selected patients with negative EBV‐DNA. We found that the average rate of EBV‐DNA positivity in lymphomas was 0.376%, and EBV‐DNA‐positive patients presented higher risk with elevated lactate dehydrogenase (LDH) and β2‐MG level, B symptoms, secondary hemophagocytic syndrome and lower objective response rate compared to EBV‐DNA‐negative patients. Multivariate analysis revealed EBV‐DNA‐positive patients had inferior progression‐free survival (PFS) and overall survival (OS) and EBV‐DNA level before treatment was related to PFS but not OS of T/NK cell lymphoma. In T/NK cell lymphoma, EBV‐DNA converting negative after treatment was correlated with better PFS but not OS, and second‐line therapy could induce more EBV‐DNA‐negative conversion compared to CHOP‐based therapy. In all, EBV‐DNA positivity before treatment can be a biomarker representing the tumour burden and an independent prognostic factor. EBV‐DNA‐negative conversion after treatment is a good prognostic factor for T/NK cell lymphomas.

Altered Immune Response to the Epstein-Barr Virus as a Prerequisite for Multiple Sclerosis.

Strong epidemiologic evidence links Epstein–Barr virus (EBV) infection and its altered immune control to multiple sclerosis (MS) development. Clinical MS onset occurs years after primary EBV infection and the mechanisms linking them remain largely unclear. This review summarizes the epidemiological evidence for this association and how the EBV specific immune control is altered in MS patients. The two main possibilities of mechanisms for this association are further discussed. Firstly, immune responses that are induced during a symptomatic primary EBV infection, namely infectious mononucleosis, might be amplified during the following years to finally cause central nervous system (CNS) inflammation and demyelination. Secondly, genetic predisposition and environmental factors might not allow for an efficient immune control of the EBV-infected B cells that might drive autoimmune T cell stimulation or CNS inflammation. These two main hypotheses for explaining the association of the EBV with MS would implicate opposite therapeutic interventions, namely either dampening CNS inflammatory EBV-reactive immune responses or strengthening them to eliminate the autoimmunity stimulating EBV-infected B cell compartment. Nevertheless, recent findings suggest that EBV is an important puzzle piece in the pathogenesis of MS, and understanding its contribution could open new treatment possibilities for this autoimmune disease.

77P Hypermethylation of genes HIST1H4F, Septin9 and RASSF1 as the potential biomarker for nasopharyngeal carcinoma screening

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southeast Asia, especially in southern China. There were about 129,000 new NPC cases and 34,000 deaths worldwide in 2018 according to Global Cancer Obsercatory. Even though NPC is sensitive to radiotherapy and has a 5-year survival rate of about 70%, the prognosis is poor in advanced stage. Therefore, it is important to screen NPC in the early stage. Epstein–Barr virus (EBV) infection plays important roles in the development of NPC, and EBV immunological assay is employed as a standard diagnostics of NPC, however, it is an invasive method.