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
Journal
Clinical Cancer Research
Journal Volume
22
Journal Issue
14
Pages
3451-3457
Date Issued
2016
Author(s)
Abstract
Purpose: 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 glycoprotein 350 (gp350), were associated with lower NPC risk. Experimental Design: 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 highrisk NPC biomarker. Results: EBV-neutralizing antibodies blocking B-cell infection and anti-gp350 antibodies were present at significantly higher levels in disease-free controls compared with incident NPC cases (P < 0.03). Family members with both low EBVneutralizing 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). Conclusions: 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. Clin Cancer Res; 22(14); 3451-7. ?2016 AACR. ? 2016 American Association for Cancer Research.
SDGs
Other Subjects
biological marker; Epstein Barr NA1 immunoglobulin A antibody; glycoprotein; glycoprotein gp 350; glycoprotein gp 350 antibody; immunoglobulin A antibody; neutralizing antibody; unclassified drug; biological marker; EBV-encoded nuclear antigen 1; Epstein Barr virus antigen; glycoprotein; immunoglobulin A; neutralizing antibody; virus antibody; adult; antibody blood level; Article; B lymphocyte; cancer risk; clinical article; cohort analysis; controlled study; disease association; epithelium cell; Epstein Barr virus infection; female; high risk population; human; human cell; male; nasopharynx carcinoma; prevalence; priority journal; prospective study; protein binding; risk assessment; Taiwan; Taiwanese; virus entry; virus neutralization; aged; B lymphocyte; blood; carcinoma; Epstein Barr virus; Epstein Barr virus infection; immunology; middle aged; nasopharynx tumor; virology; young adult; Adult; Aged; Antibodies, Neutralizing; Antibodies, Viral; B-Lymphocytes; Biomarkers; Carcinoma; Epithelial Cells; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Glycoproteins; Herpesvirus 4, Human; Humans; Immunoglobulin A; Male; Middle Aged; Nasopharyngeal Neoplasms; Prospective Studies; Young Adult
Publisher
American Association for Cancer Research Inc.
Type
journal article