Viral Capsid Antigen Research Articles

Epstein-Barr Virus: An Infrequent Pathogen of Acute Undifferentiated Febrile Illness From a Tertiary Care Hospital in Southern India.

Context: Acute undifferentiated febrile illness (AUFI) is characterized by a sudden onset of raised body temperature and is a common cause of hospital admission though not recognized as a disease state by the World Health Organization. Epstein-Barr virus (EBV) is reported to account for a significant occurrence of AUFI cases.Aim: To know the role of EBV infection as a cause of acute undifferentiated febrile illness (AUFI).Settings and design: We have used the combination of EBV serological assays to establish the role of the Epstein-Barr virus as the cause of acute undifferentiated febrile illness.Methods and material: A total of 721 suspected cases of acute undifferentiated febrile illness which were tested negative for other common causes of acute febrile illness were selected for the study. Serum samples collected from these cases were tested for the presence of the EBV viral capsid antigen (VCA) IgM antibody. All positive serum samples were tested for the presence of EBV Epstein-Barr nuclear antigen (EBNA) IgG.Statistical analysis used: Statistical analysis was performed with the help of Microsoft Excel software (Microsoft Corporation, Redmond, USA). Results: Out of 721 suspected AUFI cases tested for EBV VCA IgM antibodies, 117 samples were positive and 604 were negative. All these 117 samples were tested for EBV EBNA IgG antibodies in which 88 were positive and 29 were negative. In our study, we found that around 4% (positive for VCA IgM and negative for EBNA IgG) of AUFI cases can be attributed to primary acute EBV infection.Conclusions: EBV infection should be considered particularly in AUFI cases of less than five years of age even in those who do not meet the typical presentation of fever, lymphadenopathy and sore throat. Our study should help to raise awareness regarding the possibility of EBV infection particularly in AUFI cases. A high index of suspicion and timely diagnosis will definitely help clinicians to avoid a battery of investigations and misuse of antibiotics in cases of AUFI.

Оцінка вкладу герпесвірусної інфекції в розвиток і прогресування хронічних гломерулярних хвороб у дітей

Актуальність. Етіологія хронічних хвороб клубочкового апарату нирки на сьогодні до кінця невідома. Описано участь ряду факторів, в тому числі вірусних інфекцій. Мета дослідження: визначення антитіл до вірусу Епштейна — Барр (ВЕБ) (IgG до нуклеарного і раннього антигену (АГ), IgG і IgM до вірусного капсидного АГ), цитомегаловірусу (ЦМВ) (IgG, IgM), вірусу простого герпесу (ВПГ) (IgM, IgG), специфічних фрагментів ДНК герпес- і поліомавірусів (BKV, JCV) методом полімеразної цепної реакції в сироватці крові та тканині нирки для уточнення ролі вірусної інфекції в розвитку гломерулопатій (ГП) у дітей. Матеріали та методи. Обстежено 130 дітей з первинними і вторинними гломерулопатіями, в тому числі 42 реципієнти ниркового трансплантата, на наявність антитіл і фрагментів ДНК герпес- і поліомавірусів, як ­контроль — 36 умовно здорових дітей, проведено ультраструктурний аналіз нефробіоптатов пацієнтів з ГП. Результати. IgM до ВПГ і IgM до ЦМВ частіше виявлялися в сироватках пацієнтів із вторинними і первинними ГП порівняно з контролем (17,1 і 12,8 % проти 0, 20 і 17 % проти 5,5 % відповідно), а також дітьми з нирковим трансплантатом (проти 0 % до ВПГ, 5 % до ЦМВ і 7 % до ВЕБ відповідно). У 5 випадках з групи вторинних ГП одночасно виявлялися АТ класу М до двох і більше герпесвірусів. У 24,4 % дітей із вторинними ГП в крові були виявлені як АТ до ВЕБ (IgG до раннього АГ і IgM до вірусного капсидного АГ), ЦМВ і ВПГ (IgM), так і нуклеокапсиди ВПГ, ЦМВ і ВЕБ. Ультраструктурний аналіз 10 нефробіоптатів показав наявність ДНК ВПГ 1-го, 2-го типу в одному і ДНК ЦМВ у 2 випадках. Наведено особливості перебігу ГП, асоційованих з герпетичною інфекцією. Висновки. Герпесвіруси впливають на розвиток і перебіг патологічного процесу при хронічних ГП. Наведений алгоритм вірусологічного обстеження дітей з ГП може використовуватися в практиці нефролога.

Seroprevalence of viral infectious diseases and associated factors in Korean patients with inflammatory bowel diseases.

Background/AimsData on the immunoprotective status against measles, mumps, rubella, varicella zoster virus (VZV), hepatitis A virus (HAV), and Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) are still lacking. Therefore, we investigated the seropositivity rates for viral infectious diseases and the associated factors in Korean patients with IBD.MethodsIn this retrospective cohort study, serum immunoglobulin G antibody positivity rates against measles virus, mumps virus, rubella virus, VZV, HAV, and EBV viral capsid antigen (VCA) were measured in patients with Crohn’s disease or ulcerative colitis (UC) who first visited the IBD clinic. Seropositivity rates and their associated factors were analyzed.ResultsBetween January 2016 and December 2018, 263 patients were enrolled (male, 167 [67.3%]; UC, 134 [50.9%]). The median age at serological test was 30 years (interquartile range, 22 to 46). The seropositivity rates were 84.0%, 85.2%, 66.5%, 87.4%, 50.0%, and 93.7% for measles, mumps, rubella, VZV, HAV, and EBV, respectively. Younger age at serological test was associated with seronegative status for measles (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.88 to 0.96), VZV (aOR, 0.83; 95% CI, 0.74 to 0.93), and HAV (aOR, 0.93; 95% CI, 0.91 to 0.95). Furthermore, IBD type-UC was associated with seronegative status against VZV (aOR, 0.33; 95% CI, 0.11 to 0.99).ConclusionsSeropositivity rates for common viral infectious diseases in Korean patients with IBD were similar to those of the general population. In the younger age group, protective immunity against measles, VZV, and HAV is required, with proper vaccination, as necessary.

Acute Epstein‐Barr virus associated haemophagocytosis in an Asian female: What is the diagnosis?

Acute <scp>Epstein‐Barr</scp> virus associated haemophagocytosis in an Asian female: What is the diagnosis?

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (β = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Abstract 833: Characterization of the humoral immune response to the EBV proteome in extranodal natural killer T-cell lymphoma

Abstract Background: Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been linked to infection with Epstein-Barr virus (EBV). However, the humoral immune response to EBV in relation to NKTCL has not been well studied. Methods: We examined plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan from the multi-center hospital-based AsiaLymph case-control study using a protein microarray that measured IgG and IgA antibodies against 202 sequences across the entire EBV proteome. Internal validation was performed by using four ELISA assays targeting IgG and IgA antibodies against viral capsid antigen (VCA) and nuclear antigen 1 (EBNA1), antibodies that have previously been linked to other EBV-associated cancers and reported in NKTCL cases. Differences in the mean standardized signal intensity (SSI) for IgG and IgA antibodies against each of the array sequences between NKTCL and controls were compared using unpaired t tests. Odds ratios (ORs) and 95% CIs for the association between each three-level categorical anti-EBV antibody variable (i.e., tertiles) and NKTCL status were calculated using logistic regression models adjusted for sex, age and study area. Results: We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. NKTCL disease associations were disproportionately observed for IgG rather than IgA markers. Nine anti-EBV IgG responses were elevated in NKTCL cases compared with controls with odds ratios highest vs. lowest tertile &amp;gt; 6.0 (Bonferroni-corrected p-values&amp;lt;0.05). Among these nine responses, three (all mapping to EBNA3A) are novel and have not been found to be strongly associated with other EBV-associated tumors of B-cell or epithelial origin while six mapped to proteins (BALF2, BMRF1, BZLF1, BVRF2, and BPLF1) that have been reported previously to be associated with other EBV-associated cancers. IgG antibodies against EBNA1, which have consistently been associated with other EBV-associated tumors in different populations, were not elevated in NKTCL cases. Results from ELISA assays confirmed our array-based findings. Conclusions: Our data suggest that the anti-EBV humoral response profiles are altered in NKTCL, but that alterations observed differ from those for other EBV-associated tumors of B-cell or epithelial origin. Our findings provide clues for future NKTCL pathogenesis research. Citation Format: Zhiwei Liu, Yomani Sarathkumara, John K. Chan, Yok-Lam Kwong, Tai Hing Lam, Dennis Kai Ming Ip, Brian Chiu, Jun Xu, Yu-Chieh Su, Carla Proietti, Kelly J. Yu, Raymond Liang, Wei Hu, Bu-Tian Ji, Anna E. Coghill, Ruth M. Pfeiffer, Allan Hildesheim, Nathaniel Rothman, Denise Doolan, Qing Lan. Characterization of the humoral immune response to the EBV proteome in extranodal natural killer T-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 833.

Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

Febrile palpebral edema

Febrile palpebral edema

Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination.

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.

Jaundice as a Rare Manifestation of Epstein-Barr Virus Primary Infection

Epstein-Barr virus (EBV) primary infection usually presents with classic symptoms of infectious mononucleosis (IM) like fever, lymphadenopathies and tonsillopharyngitis. Liver damage is frequently mild and self-limited and there are only a few cases of severe EBV-induced cholestatic hepatitis and jaundice reported in the literature. The authors present the case of a 22-year-old woman who was admitted with acute fever and jaundice. Physical examination revealed posterior cervical lymphadenopathies and painful hepatosplenomegaly. Laboratorial findings suggested an obstructive cause for jaundice but ultrasound and magnetic resonance cholangiopancreatography excluded biliary duct pathology. Heterophile antibodies were negative but EBV-specific antibodies revealed isolated positive viral capsid antigen (VCA) immunoglobin (Ig) M suggesting the diagnosis of early phase of EBV primary infection. The diagnosis of EBV-induced cholestatic hepatitis was confirmed after identification of EBV deoxyribonucleic acid (DNA) in blood and by liver biopsy. Supportive management was provided and, despite an initial clinical deterioration, the patient had a favorable outcome. EBV is a virus with a high prevalence worldwide, mainly subclinical, and jaundice is a rare manifestation of the infection. Although the majority of the patients recover without sequelae, progression to liver failure has been described and a careful assessment for complications is mandatory. Therefore, EBV infection should be included in the comprehensive differential diagnosis of jaundice in all age groups.

A broadly cross-reactive monoclonal antibody against hepatitis E virus capsid antigen

To generate a hepatitis E virus (HEV) genotype 3 (HEV-3)–specific monoclonal antibody (mAb), the Escherichia coli–expressed carboxy-terminal part of its capsid protein was used to immunise BALB/c mice. The immunisation resulted in the induction of HEV-specific antibodies of high titre. The mAb G117-AA4 of IgG1 isotype was obtained showing a strong reactivity with the homologous E. coli, but also yeast-expressed capsid protein of HEV-3. The mAb strongly cross-reacted with ratHEV capsid protein derivatives produced in both expression systems and weaker with an E. coli–expressed batHEV capsid protein fragment. In addition, the mAb reacted with capsid protein derivatives of genotypes HEV-2 and HEV-4 and common vole hepatitis E virus (cvHEV), produced by the cell-free synthesis in Chinese hamster ovary (CHO) and Spodoptera frugiperda (Sf21) cell lysates. Western blot and line blot reactivity of the mAb with capsid protein derivatives of HEV-1 to HEV-4, cvHEV, ratHEV and batHEV suggested a linear epitope. Use of truncated derivatives of ratHEV capsid protein in ELISA, Western blot, and a Pepscan analysis allowed to map the epitope within a partially surface-exposed region with the amino acid sequence LYTSV. The mAb was also shown to bind to human patient–derived HEV-3 from infected cell culture and to hare HEV-3 and camel HEV-7 capsid proteins from transfected cells by immunofluorescence assay. The novel mAb may serve as a useful tool for further investigations on the pathogenesis of HEV infections and might be used for diagnostic purposes.Key points• The antibody showed cross-reactivity with capsid proteins of different hepeviruses.• The linear epitope of the antibody was mapped in a partially surface-exposed region.• The antibody detected native HEV-3 antigen in infected mammalian cells.

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.

Positive Epstein-Barr Virus Detection in Corona Virus Disease 2019 (COVID-19) Patients

Background: The pathological report suggested severe immune injury in corona virus disease 2019 (COVID-19) patients. Epstein-Barr virus (EBV) reactivation has been reported in immunocompromised individuals. We aimed to detect EBV coinfection in COVID-19 patients. Methods: In this single-centered, retrospective, observational study, COVID-19 patients were enrolled in our study. The characteristics of the demographic, symptoms, signs, laboratory and CT results and clinical outcome were collected. Data were compared between EBV seropositive and seronegative COVID-19 patients. Findings: Of 196 patients, 62 COVID-19 patients were included in our study. The median age was 37 years, with 32 (51 · 6%) females. Among these COVID-19 patients, 35 (56 · 5%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV seropositive COVID-19 patients had a 3 · 64-fold risk of having a fever symptom than EBV seronegative (95%CI, 1 · 26-10 · 51; P=0 · 02). C-reactive protein (CRP) in EBV seropositive COVID-19 patients were higher than EBV seronegative patients (P=0 · 01). The proportion of CD8 (CD8%) was statistically significant lower in EBV seropositive COVID-19 patients (P=0 · 048). The CD4/CD8 in EBV seropositive COVID-19 patients was lower than that in EBV seronegative patients (P=0 · 046). 25 (40 · 3%) were discharged before February 29, 2020. The median recovery time in EBV seropositive COVID-19 patients (24 days) was higher than that in EBV seronegative COVID-19 patients (19 days), while the difference was not significant (P=0 · 07). Interpretation: EBV acute infection was found in COVID-19 patients. EBV seropositivity was associated with fever, increased inflammation and cellular immune response in COVID-19 patients. EBV reactivation should be considered in treating COVID-19. Funding Statement: None. Declaration of Interests: The authors confirmed that no competing financial interests exist. Ethics Approval Statement: The study was approved by the ethical committee board of Renmin Hospital of Wuhan University (WDRY2020-K073).

Positive Epstein\u2013Barr virus detection in coronavirus disease 2019 (COVID-19) patients

The objective of this study was to detect the Epstein–Barr virus (EBV) coinfection in coronavirus disease 2019 (COVID-19). In this retrospective single-center study, we included 67 COVID-19 patients with onset time within 2 weeks in Renmin Hospital of Wuhan University from January 9 to February 29, 2020. Patients were divided into EBV/SARS-CoV-2 coinfection group and SARS-CoV-2 infection alone group according to the serological results of EBV, and the characteristics differences between the two groups were compared. The median age was 37 years, with 35 (52.2%) females. Among these COVID-19 patients, thirty-seven (55.2%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV/SARS-CoV-2 coinfection patients had a 3.09-fold risk of having a fever symptom than SARS-CoV-2 infection alone patients (95% CI 1.11–8.56; P = 0.03). C-reactive protein (CRP) (P = 0.02) and the aspartate aminotransferase (AST) (P = 0.04) in EBV/SARS-CoV-2 coinfection patients were higher than that in SARS-CoV-2 infection alone patients. EBV/SARS-CoV-2 coinfection patients had a higher portion of corticosteroid use than the SARS-CoV-2 infection alone patients (P = 0.03). We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.

Seroepidemiological Study of Epstein-Barr Virus in Patients with Head and Neck Tumors at Shahid Rajaee Hospital in Babolsar, Iran

Background: Epstein-Barr virus (EBV) is a herpes virus, which is the cause of infectious mononucleosis. Seroepidemiological studies show that more than 95% of adults in the world are infected with this virus. This virus is a modifying virus that is associated with some malignancies such as Burkitt lymphoma, tumors in HIV-infected patients, Hodgkin's lymphoma, head and neck tumors, and T-cell lymphoma. Objectives: This study aimed to determine the prevalence of EBV and its relation to the type of cancer in patients with head and neck tumors, which were treated in the years 2015 to 2016 at Shahid Rajaee Radiation Hospital in Babolsar. Methods: During one year, all patients with head and neck tumors were monitored, and finally, a total of 37 patients who had pathologically confirmed diagnoses were entered into the study after obtaining written informed consent. In this descriptive study, specific anti-EBV viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA). Also, other patients' information was obtained from their records. Results: The mean age of the patients was 59 years, and the number of men (70.23%) was higher than that of women (29.77%). Regarding the histopathology information and the frequency of tumors, most of the patients had squamous cell carcinoma (SCC) (73%) in the sites of the nasopharynx (27.02%) and pharynx (18.91%). The results of the ELISA test showed that IgG antibodies were positive in most of the patients (86.5 %). About the relation between the sites of the tumors and the IgG antibody, all patients (100%) with nasopharyngeal, tongue, and lips cancers were positive while they were the least in pharyngeal cancer (5.4%). Conclusions: This study showed that a significant number of patients with head and neck tumors (86.5%) were infected with this virus, which indicates that EBV as a carcinogenic agent in head and neck tumors has a high prevalence in our society and requires preventive and therapeutic actions.

Characteristics of primary Epstein-Barr virus infection disease spectrum and its reactivation in children, in Suzhou, China.

Epstein-Barr virus (EBV) is a globally prevalent herpesvirus associated with multiple diseases. This study aimed to determine the characteristics of primary EBV infection disease spectrum and reactivation in children, in Suzhou, China. All children admitted to the Children's Hospital of Soochow University between May 2018 and September 2020 with suspected EBV-associated disease and subjected to the indirect immunofluorescence assay for EBV-specific antibodies and plasma EBV-DNA assays were included. Of the 3567 children, 2782 (78.0%) tested positive for EBV. The positive rates of viral capsid antigen (VCA)-IgM, VCA-IgG, early antigen (EA)-IgG, nuclear antigen (EBNA)-IgG, and plasma EBV-DNA were 12.1%, 74.6%, 37.9%, 35.6%, and 31.1%, respectively. The lowest VCA-IgG and EBNA-IgG seropositivity rates occurred at ages between 8 and 36 months, then increased gradually in the older age groups. The EBV-IgM seropositivity rate was the highest in those aged 36 to <72 months. Primary EBV infection was more common in children aged 36 to <72 months. In past infections, reactivation mainly occurred in 8 to <36 months. The most common disease caused by primary EBV infection was infectious mononucleosis (56.1%), followed by a respiratory infection (17.0%). Respiratory infection (30.0%), EBV infection (29.2%), and hemophagocytic lymphohistiocytosis (HLH) (15.8%) were the commonest diseases caused by EBV reactivation. EBV reactivation was a risk factor for HLH (adjusted odds ratio, 16.4; 95% confidence interval, 7.9-34.0). Among reactivated patients, the viral load of HLH was higher than that of EBV infection and respiratory infection (p < .01). This is a retrospective large sample study that explored the characteristics of primary EBV infection disease spectrum and reactivation in children.

The Association of Single-Nucleotide Polymorphism rs13181 in ERCC2 with Risk and Prognosis of Nasopharyngeal Carcinoma in an Endemic Chinese Population.

ObjectiveWe examined whether the single-nucleotide polymorphism (SNP) rs13181 in the gene encoding excision repair cross complementation group 2 (ERCC2) is associated with the risk and prognosis of nasopharyngeal carcinoma (NPC).MethodsSNPs at rs13181 were genotyped in 439 NPC patients (NPC group) and 431 age- and gender-matched cancer-free controls (control group) from a region of China where NPC is endemic, and frequencies of GG, GT and TT genotypes were compared between the two groups in the case–control study. In a subset of 365 NPC cases, SNPs were examined for potential correlation with tumor-free survival time (TFS) and overall survival (OS).ResultsRelative to NPC risk with a TT genotype, NPC risk was similar with GT + GG genotypes (OR 1.052, 95% CI 0.656–1.688), after adjusting for gender, age, smoking history, and immunoglobin A against Epstein-Barr virus capsid antigen (EBV-VCA-IgA) status. Univariate analysis showed that the GG or GT genotype was associated with significantly worse TFS (p<0.001) and OS (p=0.010) than the TT genotype. Prognosis was significantly worse for men than for women (TFS, p=0.045; OS, p=0.031), for T3–T4 classification than for T1–T2 (TFS, p=0.009; OS, p=0.007), for N3 than for N0+N1+N2 (TFS, p<0.001; OS, p<0.001). Based on multivariate analysis, independent risk factors for poor TFS were GG or GT genotype (HR 2.629, 95% CI 1.625–4.254, p<0.001), T3–T4 classification (HR 2.146, 95% CI 1.244–3.701, p=0.006) and N3 (HR 2.527, 95% CI 1.574–4.059, p<0.001). GG or GT genotype (HR 2.217, 95% CI 1.283–3.832, p=0.004), gender (HR 1.989, 95% CI 1.046–3.785, p=0.036), T3–T4 (HR 2.431, 95% CI 1.306–4.526, p=0.005) and N3 (HR 2.693, 95% CI 1.637–4.432, p<0.001) were independent risk factors for poor OS.ConclusionThe rs13181 SNP in ERCC2 does not appear to be associated with NPC risk, but it may serve as an independent prognostic factor for NPC recurrence and death.

Determination and Role of Epstein-Barr Virus in Patients With Lymphoproliferative Disorders

IntroductionEpstein-Barr virus (EBV) is associated with different types of human malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and lymphomas. We retrospectively investigated the presence of EBV-DNA by real-time PCR in clinical samples of patients diagnosed as having hematologic malignancies while investigating the cause of lymphoproliferative disorders, and investigated its relationship to clinical manifestations. Patients and MethodsFifty clinical samples sent to Gazi University’s hematology clinics between November 2013 and March 2018 were included. EBV-DNA was investigated by real-time PCR method, and EBV-IgM and EBV-IgG antibodies were investigated by ELISA. ResultsFifty serum samples were investigated, and 10% (5/50) EBV-DNA positivity was determined in patients. Of the 5 patients with EBV-DNA positivity, 2 had acute lymphoblastic leukemia, 1 lymphoma, 1 T-cell lymphoma, and 1 B-cell lymphoma. Concomitant EBV-DNA and viral capsid antigen (VCA)-IgM positivity was not detected. The VCA-lgM test results of the all EBV-DNA–positive patients were negative and VCA-IgG positive (except for 1 patient). Regarding virus load, of the 5 samples, 2, 1, 1, and 1 of the samples had a virus load of 102, 103, 104, and 105 copies/mL, respectively. ConclusionEBV infection is threatening in patients with hematologic malignancies and are diagnosed by serologic and molecular methods. As a result of the study, we suggest that the detection of EBV-DNA by real-time PCR in patients being admitted with lymphoproliferative diseases and diagnosed as acute lymphoblastic leukemia and lymphomas may be useful in follow-up and treatment.

Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population

BackgroundThe role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders.MethodsUsing data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3.ResultsHigher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed.ConclusionOur study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.

Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia

Cognitive deficits are a central feature of schizophrenia whose etiology is not fully understood. Epstein Barr Virus (EBV) is a potentially neurotropic infectious agent that can generate persistent infections with immunomodulatory effects. Previous studies have found an association between EBV antibodies and cognitive functioning in different populations, but there has been limited investigation in schizophrenia. In this study, 84 individuals with schizophrenia were administered a comprehensive neuropsychological battery, the MATRICS Consensus Cognitive Battery (MCCB). Participants also provided a blood sample, from which antibodies to the EBV whole virion and specific proteins were measured. Multivariate models were constructed to determine the association between these antibodies and cognitive performance on the MCCB overall and domain scores. Using these models, we found a significant association between the MCCB overall percent composite score and level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. A significant association was also found for the MCCB social cognition domain with the level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. In all cases, a higher level of antibodies was associated with a lower level cognitive performance. These findings suggest that exposure to EBV may contribute to cognitive deficits in schizophrenia, a finding which may have implications for new methods of prevention and treatment.