Patterns of inter-individual variability in the antibody repertoire targeting proteins across the Epstein-Barr virus proteome

Liu, Zhiwei, Coghill, Anna E., Pfeiffer, Ruth M., Proietti, Carla, Hsu, Wan-Lun, Chien, Yin-Chu, Lekieffre, Lea, Krause, Lutz, Yu, Kelly J., Lou, Pei-Jen, Wang, Cheng-Ping, Mulvenna, Jason, Middledorp, Jaap M., Bethony, Jeff, Chen, Chien-Jen, Doolan, Denise L., and Hildesheim, Allan (2018) Patterns of inter-individual variability in the antibody repertoire targeting proteins across the Epstein-Barr virus proteome. Journal of Infectious Diseases, 217. pp. 1923-1931.

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Background: Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV)proteins and how such patterns inform disease risk. Methods: We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses. Results: Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10–46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test–combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk. Conclusions: These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.

Item ID: 56608
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: antibody microarray, antibody response, Epstein-Barr virus, Taiwan, Iga, IgG
Copyright Information: Copyright © 2018 Oxford University Press
Funders: National Cancer Institute (NCI), National Health and Medical Research Council (NHMRC), National Science Council of Taiwan
Date Deposited: 17 Dec 2018 04:58
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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