Abstract 833: Characterization of the humoral immune response to the EBV proteome in extranodal natural killer T-cell lymphoma
Authors: Liu Zhiwei , Sarathkumara Yomani , Chan John K. , Kwong Yok-Lam , Lam Tai Hing , Ip Dennis Kai Ming , Chiu Brian , Xu Jun , Su Yu-Chieh , Proietti Carla , Yu Kelly J. , Liang Raymond , Hu Wei , Ji Bu-Tian , Coghill Anna E. , Pfeiffer Ruth M. , Hildesheim Allan , Rothman Nathaniel , Doolan Denise , Lan Qing 
Published: July 2021

Abstract
Background: Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been linked to infection with Epstein-Barr virus (EBV). However, the humoral immune response to EBV in relation to NKTCL has not been well studied.
Methods: We examined plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan from the multi-center hospital-based AsiaLymph case-control study using a protein microarray that measured IgG and IgA antibodies against 202 sequences across the entire EBV proteome. Internal validation was performed by using four ELISA assays targeting IgG and IgA antibodies against viral capsid antigen (VCA) and nuclear antigen 1 (EBNA1), antibodies that have previously been linked to other EBV-associated cancers and reported in NKTCL cases. Differences in the mean standardized signal intensity (SSI) for IgG and IgA antibodies against each of the array sequences between NKTCL and controls were compared using unpaired t tests. Odds ratios (ORs) and 95% CIs for the association between each three-level categorical anti-EBV antibody variable (i.e., tertiles) and NKTCL status were calculated using logistic regression models adjusted for sex, age and study area.
Results: We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. NKTCL disease associations were disproportionately observed for IgG rather than IgA markers. Nine anti-EBV IgG responses were elevated in NKTCL cases compared with controls with odds ratios highest vs. lowest tertile &gt; 6.0 (Bonferroni-corrected p-values&lt;0.05). Among these nine responses, three (all mapping to EBNA3A) are novel and have not been found to be strongly associated with other EBV-associated tumors of B-cell or epithelial origin while six mapped to proteins (BALF2, BMRF1, BZLF1, BVRF2, and BPLF1) that have been reported previously to be associated with other EBV-associated cancers. IgG antibodies against EBNA1, which have consistently been associated with other EBV-associated tumors in different populations, were not elevated in NKTCL cases. Results from ELISA assays confirmed our array-based findings.
Conclusions: Our data suggest that the anti-EBV humoral response profiles are altered in NKTCL, but that alterations observed differ from those for other EBV-associated tumors of B-cell or epithelial origin. Our findings provide clues for future NKTCL pathogenesis research.
Citation Format: Zhiwei Liu, Yomani Sarathkumara, John K. Chan, Yok-Lam Kwong, Tai Hing Lam, Dennis Kai Ming Ip, Brian Chiu, Jun Xu, Yu-Chieh Su, Carla Proietti, Kelly J. Yu, Raymond Liang, Wei Hu, Bu-Tian Ji, Anna E. Coghill, Ruth M. Pfeiffer, Allan Hildesheim, Nathaniel Rothman, Denise Doolan, Qing Lan. Characterization of the humoral immune response to the EBV proteome in extranodal natural killer T-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 833.