Comparative analysis of the humoral immune response to the EBV proteome across EBV-related malignancies

Argirion, I. et al. (2023) Comparative analysis of the humoral immune response to the EBV proteome across EBV-related malignancies. Cancer Epidemiology, Biomarkers and Prevention, (doi: 10.1158/1055-9965.EPI-22-0452) (PMID:36788424) (Early Online Publication)

Abstract

Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Conclusion: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jarrett, Professor Ruth
• Authors: Argirion, I., Pfeiffer, R. M., Proietti, C., Coghill, A. E., Yu, K. J., Middeldorp, J. M., Sarathkumara, Y. D., Hsu, W.-L., Chien, Y.-C., Lou, P.-J., Wang, C.-P., Rothman, N., Lan, Q., Chen, C.-J., Mbulaiteye, S. M., Jarrett, R. F., Glimelius, I., Smedby, K. E., Hjalgrim, H., Hildesheim, A., Doolan, D. L., and Liu, Z.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cancer Epidemiology, Biomarkers and Prevention
• Publisher: American Association for Cancer Research
• ISSN: 1055-9965
• ISSN (Online): 1538-7755
• Published Online: 14 February 2023
• Copyright Holders: Copyright © 2023 American Association for Cancer Research
• First Published: First published in Cancer Epidemiology, Biomarkers and Prevention 2023
• Publisher Policy: Reproduced in accordance with the publisher copyright policy