Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.

The value of circulating CYFRA21-1 expression in patients with nasopharyngeal carcinoma: a study of 529 subjects.

BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) needs more reliable biomarkers. The aim of this study was to investigate serum cytokeratin 19 fragment 21.1 (CYFRA21-1) as an NPC biomarker based on data from a large sample. METHODS: From October 2010 to February 2014, 529 subjects were enrolled and divided into three groups-NPC group (n = 274), healthy control group (n = 175) and nasal inflammatory disease group (n = 80). Serum CYFRA21-1 levels were measured prior to radiotherapy/chemoradiotherapy, and their associations with T, N, and clinical classification were determined. Receiver operating characteristic curve analysis was performed to discriminate the NPC group from the healthy control and nasal inflammatory disease groups. Three Epstein-Barr virus (EBV) antibodies and their correlations with serum CYFRA21-1 levels were analyzed. RESULTS: Pretreatment serum CYFRA21-1 levels were significantly elevated in the NPC group compared with the other groups (p < 0.01), Furthermore, serum CYFRA21-1 levels decreased significantly after radiotherapy (p < 0.01). Serum CYFRA21-1 levels were closely related to T, N, and clinical classifications. The area under the curve, sensitivity and specificity of the serum CYFRA21-1 levels in the NPC patients were 0.89, 0.87 and 0.83, respectively. Strong correlations were observed between serum CYFRA21-1 levels and EBV antibodies. CONCLUSION: Serum CYFRA21-1 may be a reliable and effective biomarker for NPC.

Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). RESULTS: Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis-free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). CONCLUSION: Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Associations between environmental factors and serological Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma in South China.

Epstein-Barr virus (EBV) reactivation, reflected by aberrantly increased levels of various serological antibodies, has been suggested to be an early indicator of nasopharyngeal carcinoma (NPC) onset and progression. We have previously suggested that certain lifestyle and dietary factors were associated with elevated serological levels of the antibody against various EBV antigens namely VCA, Zta, EBNA1, and oral EBV DNA loads among healthy population. It remains unclear whether these potential environmental factors would also influence EBV serological antibodies in NPC patients. We conducted an epidemiological study to evaluate the associations between such environmental factors and EBV antibody levels among 1701 NPC patients in South China. Pretreatment serums were collected and examined for VCA-IgA and EA-IgA by immunoenzymatic assays and antienzyme rate (AER) of EBV DNase-specific neutralizing antibody. We found that consumption of Canton-style herbal tea was significantly correlated with increased serological antibody levels of VCA-IgA and EA-IgA, with adjusted ORs of 1.35 (95% CI: 1.03-1.76) and 1.32 (95% CI: 1.01-1.73), respectively, in the weekly intake frequency stratum, while not related to AER of EBV DNase-specific neutralizing antibody. Smoking was found to be not only an apparent risk factor for higher antibody levels of AER in stage III-IV patients (OR = 1.60, 95% CI: 1.11-2.30), but also associated closely with NPC stage at diagnosis (OR = 2.17, 95% CI: 1.47-3.22), with dose-response effects. In conclusion, we found consumption of Canton-style herbal tea and cigarette smoking were in positive associations with elevated EBV antibodies in NPC patients, which may be of public health significance for the primary prevention of EBV-associated diseases especially NPC.

The Relationship Between Environmental Factors and the Profile of Epstein-Barr Virus Antibodies in the Lytic and Latent Infection Periods in Healthy Populations from Endemic and Non-Endemic Nasopharyngeal Carcinoma Areas in China.

Our previous study found that smoking was associated with an elevated level of the antibody against VCA in the Epstein-Barr virus (EBV) lytic phase, which was an important predictive marker of the risk of nasopharyngeal carcinoma (NPC). It remained unknown whether environmental factors were associated with the levels of other EBV antibodies, such as Zta-IgA, EA-IgA, EBNA1-IgA, and LMP1-IgA, in the lytic and latent infection periods. We aimed to investigate the possible environmental inducers that could affect EBV antibody levels in two independent healthy male populations from endemic NPC areas in South China (N=1498) and non-endemic NPC areas in North China (N=1961). We performed ELISA and immunoenzymatic assays to test the levels of antibodies specific to the EBV antigens. The seropositive rates of antibodies against the antigens expressed in both the EBV latent and lytic infection periods, namely, LMP1-IgA, EBNA1-IgA, and Zta-IgA, in endemic areas (28.65%, 5.43% and 14.49%, respectively) were significantly higher than those in non-endemic areas (14.43%, 1.07% and 6.32%, respectively). Smoking was associated with higher seropositivity for EBNA1-IgA (OR=1.47, 95% CI=1.12-1.93) and Zta-IgA (OR=1.28, 95% CI=0.99-1.66), with dose-response effects, while not associated with the levels of LMP1-IgA. In conclusion, smoking was an important environmental factor, which associated with increased levels of EBNA1-IgA, and Zta-IgA.

Riesgo de complicaciones virales postrasplante en candidatos a trasplante renal con donante vivo / Risk of viral post-transplant complications in living donor kidney transplant candidates

Introducción: El trasplante renal con donante vivo se promueve en Cuba y en el resto del mundo. La definición del riesgo de complicaciones postrasplante por citomegalovirus (CMV) y virus de Epstein Barr (EBV) es parte de las pruebas de compatibilidad pretrasplante. Objetivo: Determinar el riesgo de complicaciones postrasplante con estos virus en pacientes cubanos candidatos a trasplante renal con donante vivo. Método: Se determinaron anticuerpos IgG anti-CMV e IgG anti-EBV por ensayo de inmunoabsorción ligado a enzima en 301 muestras de candidatos a TRDV y 390 de posibles donantes recibidas, entre julio de 2013 y julio de 2019, en el laboratorio de Histocompatibilidad del Instituto de Hematología e Inmunología. Resultados: En los candidatos a trasplante renal con donante vivo la seroprevalencia del EBV fue mayor que la del CMV y ambas aumentaron con la edad. El 100 % de los pacientes de grupo sanguíneo AB tuvieron EBV y CMV. No existió dependencia entre los anticuerpos anti-EBV y anti-CMV con los anticuerpos anti-HLA, la edad, sexo, color de la piel, grupo sanguíneo, hepatitis B y C, tipo de diálisis, trasplantes y transfusiones previas. El 7,3 % de los pacientes presentaron alto riesgo de complicaciones postrasplante. Conclusiones: La seroprevalencia de CMV y EBV en los candidatos a trasplante renal con donante vivo cubanos es alta, por lo que pocos tienen riesgo alto de complicaciones postrasplantes debido a estos virus(AU)

Introduction: Living donor kidney transplant is promoted in our country and the rest of the world. The definition of Cytomegalovirus (CMV) and Epstein Barr virus (EBV) post-transplant complications risk is part of pretransplant compatibility tests. Objective: To assess post-transplant complication risk with these viruses in Cuban candidates to living donor kidney transplant. Methods: Detection of IgG anti-CMV and IgG anti-EBV antibodies by enzyme-linked immunoabsorbent assay was performed on 301 receptors and 390 living donors' serum examples received, from July 2013 to July 2019, at the Histocompatibility department of the Institute of Hematology and Immunology. Results: In candidates to living donor kidney transplant, EBV seroprevalence was greater than CMV's and increased with age. The 100% of AB blood group had CMV and EBV. There was no association between IgG anti-CMV and IgG anti-EBV antibodies and anti-HLA antibodies, age, gender, skin color, blood group, hepatitis B and C, dialysis type, previous transplants, and transfusions. The 7.3% of patients were labeled as post-transplant complications high risk. Conclusions: The seroprevalence of CMV and EBV in living donor kidney transplant Cuban candidates is high, that´s why patients with high risk for post-transplant complications due to these viruses are a few(AU)

Early developmental exposures shape trade-offs between acquired and innate immunity in humans.

BACKGROUND AND OBJECTIVES: Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. METHODOLOGY: We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein-Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants' birth (1983-4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. RESULTS: In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. CONCLUSIONS AND IMPLICATIONS: Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women.