Journal Article

Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma

Kwong, Yok-Lam, Chiu, Brian C.-H., Doolan, Denise L., Yu, Kelly J., Bassig, Bryan, Hildesheim, Allan, Pfeiffer, Ruth M., Liu, Zhiwei, Cooper, Martha M., Ji, Bu-Tian, Liang, Raymond, Coghill, Anna E., Lan, Qing, Su, Yu-Chieh, Sarathkumara, Yomani D., Xu, Jun, Proietti, Carla, Hu, Wei, Rothman, Nathaniel, Chan, John K. C., Lam, Tai Hing, Ip, Dennis Kai Ming

2021

Overview

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORs highest vs. lowest tertile  > 6.0 (Bonferroni-corrected P -values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/254 / 631/67/1990/291/1621/1916 / 631/67/2324 / Adult / Aged / Aged, 80 and over / Antibodies / Antibodies, Viral - immunology / Antibody response / Case-Control Studies / Disease Susceptibility / DNA microarrays / Enzyme-Linked Immunosorbent Assay / Epstein-Barr virus / Epstein-Barr Virus Infections - complications / Epstein-Barr Virus Infections - immunology / Epstein-Barr Virus Infections - virology / Female / Herpesvirus 4, Human - genetics / Herpesvirus 4, Human - immunology / Herpesvirus 4, Human - metabolism / Hong Kong / Host-Pathogen Interactions - immunology / Humanities and Social Sciences / Humans / Immune response / Immune response (humoral) / Immunity, Humoral / Immunoglobulin A / Immunoglobulin G / Immunoglobulin G - immunology / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, Extranodal NK-T-Cell - etiology / Lymphoma, Extranodal NK-T-Cell - pathology / Male / Malignancy / Middle Aged / multidisciplinary / Natural killer cells / Odds Ratio / Patients / Protein Array Analysis / Protein arrays / Proteomes / Quality control / Science / Science (multidisciplinary) / Serology / T-cell lymphoma / Taiwan / Tumors / Viral Proteins - immunology / Viral Proteins - metabolism / Young Adult