Zhiwei Liu1, Anna E Coghill1, Ruth M Pfeiffer1, Carla Proietti2,3, Wan-Lun Hsu4,5, Yin-Chu Chien4,6, Lea Lekieffre2, Lutz Krause2, Kelly J Yu1, Pei-Jen Lou7, Cheng-Ping Wang7, Jason Mulvenna2, Jaap M Middeldorp8, Jeff Bethony9, Chien-Jen Chen4,5, Denise L Doolan2,3, Allan Hildesheim1. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. 2. QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia. 3. Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia. 4. Genomics Research Center, Academia Sinica, Taipei. 5. Graduate Institute of Epidemiology and Prevention Medicine, College of Public Health, National Taiwan University, Taipei. 6. National Institute of Cancer Research, National Health Research Institute, Miaoli, Taiwan. 7. Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei. 8. Department of Pathology, VU University Medical Center, Amsterdam, Netherlands. 9. Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Washington, D. C.
Abstract
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.
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.
Authors: Allan Hildesheim; Denise L Doolan; Anna E Coghill; Ruth M Pfeiffer; Carla Proietti; Wan-Lun Hsu; Yin-Chu Chien; Lea Lekieffre; Lutz Krause; Andy Teng; Jocelyn Pablo; Kelly J Yu; Pei-Jen Lou; Cheng-Ping Wang; Zhiwei Liu; Chien-Jen Chen; Jaap Middeldorp; Jason Mulvenna; Jeff Bethony Journal: Clin Cancer Res Date: 2018-01-04 Impact factor: 12.531
Authors: Jajah Fachiroh; Tabitha Schouten; Bambang Hariwiyanto; Dewi K Paramita; Ahmad Harijadi; Sofia M Haryana; Mun H Ng; Jaap M Middeldorp Journal: J Infect Dis Date: 2004-05-26 Impact factor: 5.226
Authors: Anna E Coghill; Carla Proietti; Allan Hildesheim; Denise L Doolan; Sam M Mbulaiteye; Zhiwei Liu; Lutz Krause; Jeff Bethony; Ludmila Prokunina-Olsson; Adeola Obajemu; Francis Nkrumah; Robert J Biggar; Kishor Bhatia Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-10-16 Impact factor: 4.254
Authors: Zhiwei Liu; Yomani D Sarathkumara; John K C Chan; Yok-Lam Kwong; Tai Hing Lam; Dennis Kai Ming Ip; Brian C-H Chiu; Jun Xu; Yu-Chieh Su; Carla Proietti; Martha M Cooper; Kelly J Yu; Bryan Bassig; Raymond Liang; Wei Hu; Bu-Tian Ji; Anna E Coghill; Ruth M Pfeiffer; Allan Hildesheim; Nathaniel Rothman; Denise L Doolan; Qing Lan Journal: Sci Rep Date: 2021-12-08 Impact factor: 4.996