TY - JOUR
T1 - Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies
AU - Argirion, Ilona
AU - Pfeiffer, Ruth M.
AU - Proietti, Carla
AU - Coghill, Anna E.
AU - Yu, Kelly J.
AU - Middeldorp, Jaap M.
AU - Sarathkumara, Yomani D.
AU - Hsu, Wan-Lun
AU - Chien, Yin-Chu
AU - Lou, Pei-Jen
AU - Wang, Cheng-Ping
AU - Rothman, Nathaniel
AU - Lan, Qing
AU - Chen, Chien-Jen
AU - Mbulaiteye, Sam M.
AU - Jarrett, Ruth F.
AU - Glimelius, Ingrid
AU - Smedby, Karin E.
AU - Hjalgrim, Henrik
AU - Hildesheim, Allan
AU - Doolan, Denise L.
AU - Liu, Zhiwei
N1 - Funding Information: C.J. Chen reports grants from Ministry of Science and Technology during the conduct of the study. I. Glimelius reports other support from Takeda; and other support from Jansen Cilag outside the submitted work. No disclosures were reported by the other authors. Funding Information: A. Hildesheim was awarded funding from the Intramural Research Program of the NCI. This work was supported by the Intramural Research Program of NCI, USA. We are grateful to the study subjects without whom this work would not be possible. We thank Dr. Ellen T. Chang for comments on the manuscript. Publisher Copyright: ©2023 American Association for Cancer Research.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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. CONCLUSIONS: 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.
AB - 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. CONCLUSIONS: 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.
UR - http://www.scopus.com/inward/record.url?scp=85159245724&partnerID=8YFLogxK
U2 - https://doi.org/10.1158/1055-9965.EPI-22-0452
DO - https://doi.org/10.1158/1055-9965.EPI-22-0452
M3 - Article
C2 - 36788424
SN - 1055-9965
VL - 32
SP - 687
EP - 696
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -