The Epstein-Barr Virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases

Xu, Jingwu; Ahmad, Ali; Blagdon, Marie; D’Addario, Mario; Jones, James F.; Dolcetti, Riccardo; Vaccher, Emanuela; Prasad, U.; Menezes, José

doi:10.1002/(sici)1097-0215(19981023)79:5<481::aid-ijc6>3.0.co;2-x

Cited by 29 publications

(11 citation statements)

References 30 publications

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“…This complements prior cross-sectional studies that evaluated anti-gp350 antibody as a diagnostic rather than a predictive tool for NPC. IgG/IgA antibodies measured cross-sectionally were elevated in blood drawn from prevalent NPC cases compared to healthy individuals,(38, 39) consistent with our observations. This pattern was further supported by our observation of higher anti-gp350 titers in 3 patients with blood drawn within approximately one year of NPC diagnosis, compared to anti-gp350 titers in 18 incident NPC cases with blood drawn an average of 5 years prior to disease.…”

Section: Discussionsupporting

confidence: 89%

“…Some studies of gp350 vaccines in cottontop tamarins reported a lack of correlation between vaccine-induced EBV neutralizing antibody and protection against EBV-related lymphomas, suggesting that other immune responses may be important. (40) For example, anti-gp350 antibodies in human sera may have a role in antibody-dependent cellular cytotoxcitiy,(39, 41)…”

Section: Discussionmentioning

confidence: 99%

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High Levels of Antibody that Neutralize B-cell Infection of Epstein–Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma

Coghill

Nguyen

et al. 2016

Clinical Cancer Research

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Background Elevated IgA antibodies indicative of ongoing exposure to Epstein Barr virus (EBV) are high-risk biomarkers for nasopharyngeal carcinoma (NPC), an EBV-related epithelial tumor. However, protective biomarkers that limit exposure to the virus have not been defined. We evaluated whether antibodies that can neutralize EBV infection by targeting glycoproteins involved in viral cell entry, including EBV vaccine candidate glycoprotein350, were associated with lower NPC risk. Methods In a prospective cohort of 2,557 individuals from 358 high-risk NPC multiplex families in Taiwan, we identified 21 incident NPC cases and 50 disease-free controls. To complement data from high-risk families, we further identified 30 prevalent NPC cases and 50 healthy controls from the general Taiwanese population. We quantified EBV neutralizing antibody, antibodies against EBV glycoproteins involved in B-cell and epithelial cell entry, and anti-EBNA1 IgA, a high-risk NPC biomarker. Results EBV neutralizing antibodies blocking B-cell infection and anti-EBVgp350 antibodies were present at significantly higher levels in disease-free controls compared to incident NPC cases (P<0.03). Family members with both low EBV neutralizing potential and elevated EBNA1 IgA had a 7-fold increased risk of NPC (95%CI=1.9–28.7). Neutralizing antibodies against epithelial cell infection did not differ between incident cases and disease-free controls. Anti-glycoprotein antibody levels measured at diagnosis (prevalent NPC) were significantly higher than levels measured prior to diagnosis (P<0.01). Conclusion Elevated titers of EBV neutralizing antibody and anti-gp350 antibody were low-risk biomarkers for NPC. These data suggest that a vaccine that induces potent EBV gp350 and B-cell neutralizing antibodies could reduce the risk of EBV-related cancers such as NPC.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

High Levels of Antibody that Neutralize B-cell Infection of Epstein–Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma

Coghill

Nguyen

et al. 2016

Clinical Cancer Research

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“…Neutralizing antibodies are an important component of the humoral immune response and have been implicated in controlling the progression of herpesvirus-associated disease [10]. Their role in controlling KSHV infection and KSHV-associated disease is still not clear.…”

Section: Introductionmentioning

confidence: 99%

Higher Levels of Neutralizing Antibodies against KSHV in KS Patients Compared to Asymptomatic Individuals from Zambia

Kumar

Kuwa

Minhas³

et al. 2013

PLoS ONE

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Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi Sarcoma (KS), the most common cancer diagnosed in HIV- infected patients. The role of neutralizing antibodies in KS pathogenesis and in KSHV infected individuals is not clearly understood. The goal of this study was to investigate and compare the prevalence and titers of neutralizing antibodies in plasma samples from KS patients and KSHV infected asymptomatic individuals from Zambia, a KS endemic region in sub-Saharan Africa. Plasma samples (N = 267) consisting of KS patients (group 1) and asymptomatic individuals (group 2) were collected from Lusaka, Zambia. A flow cytometry based quantitative neutralization assay utilizing recombinant KSHV expressing GFP was used to detect KSHV neutralizing antibodies. Our results show that the overall prevalence of neutralizing antibodies in KS patients (group 1) was 66.7% which was significantly higher than the prevalence of 6.5% present in KSHV infected asymptomatic individuals (group 2). Total antibody titers as well as neutralizing antibodies titers were found to be significantly higher among KS patients. It is likely that higher neutralizing antibodies prevalence and titers in KS patients result from higher levels of antigenic stimulation over time. This study is first to compare prevalence and titers of neutralizing antibodies in participants with and without disease from a KSHV endemic region.

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“…The application of EBV glycoproteins in NPC screening has also been previously reported. gp350/220 induces a strong immune response in EBV-infected individuals, and several studies have detected IgA-gp350/220 in NPC patients at higher titers than in healthy controls [ 27 , 28 ]. Although the function of gp78 remains unknown, the sensitivities and specificities of IgA-gp78 and IgG-gp78 have both exceeded 70% as reported by Gu, et al [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

Zeng

et al. 2016

Oncotarget

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To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.

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The Epstein-Barr Virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases

Cited by 29 publications

References 30 publications

High Levels of Antibody that Neutralize B-cell Infection of Epstein–Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma

High Levels of Antibody that Neutralize B-cell Infection of Epstein–Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma

Higher Levels of Neutralizing Antibodies against KSHV in KS Patients Compared to Asymptomatic Individuals from Zambia

Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

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