High IgG titers against EBV glycoprotein 42 correlate with lower risk of nasopharyngeal carcinoma
Benjamin E. Warner, Kathy H.Y. Shair
Benjamin E. Warner, Kathy H.Y. Shair
Published February 17, 2025
Citation Information: J Clin Invest. 2025;135(4):e189207. https://doi.org/10.1172/JCI189207.
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Commentary

High IgG titers against EBV glycoprotein 42 correlate with lower risk of nasopharyngeal carcinoma

Abstract

Serologic biomarkers for the early diagnosis of EBV-associated nasopharyngeal carcinoma (NPC) have been identified from population studies, but a protective antibody signature in cancer-free seropositive carriers remains undefined. In this issue of the JCI, Kong et al. show that high levels of IgG against EBV glycoprotein 42 (gp42) were associated with reduced NPC risk in three independent prospective cohorts from southern China. EBV virions contain gp42, which complexes with gH-gL to facilitate fusion with B cells by binding to HLA class II (HLA-II). In this study, HLA-II was detected on non-antigen-presenting cells in a proportion of premalignant nasopharyngeal tissues, which may prime the nasopharyngeal epithelium for infection. In vitro, HLA-II expression in a nasopharyngeal cell line encouraged infection by EBV derived from B cells or epithelial cells. These findings suggest that a vaccine that stimulates gp42-IgG production may reduce the risk of EBV-associated NPC in endemic regions.

Authors

Benjamin E. Warner, Kathy H.Y. Shair

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Figure 1

Elevated levels of gp42-IgG are associated with a reduced risk of NPC.

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Elevated levels of gp42-IgG are associated with a reduced risk of NPC. (...
(A) Serologic screen of incident NPC and matched healthy controls (1:3 ratio) from three independent prospective cohorts demonstrated individuals with higher titers of IgG against EBV gp42 (gp42-IgG) had a lower risk of NPC diagnosis. (B) Alternate replication in stratified epithelial cells and B cells produce virions that selectively target the reciprocal cell type. Kong and co-authors proposed that HLA-II primes the premalignant tissue for infection by three-part virions produced in the oral and nasal epithelium (9). In this model, abundant gp42-IgG could reduce the risk of EBV infection by interfering with membrane fusion.