Patterns of Interindividual Variability in the Antibody Repertoire Targeting Proteins Across the Epstein-Barr Virus Proteome
Journal
Journal of Infectious Diseases
Journal Volume
217
Journal Issue
12
Pages
1923-1931
Date Issued
2018
Author(s)
Liu Z
Coghill A.E
Pfeiffer R.M
Proietti C
Hsu W.-L
Chien Y.-C
Lekieffre L
Krause L
Yu K.J
Mulvenna J
Middeldorp J.M
Bethony J
Chen C.-J
Doolan D.L
Hildesheim A.
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. ? 2018 The Author(s).
SDGs
Other Subjects
immunoglobulin A antibody; immunoglobulin G antibody; proteome; virus glycoprotein; immunoglobulin A; immunoglobulin G; proteome; virus antibody; virus antigen; adult; amino acid sequence; antibody response; Article; biological variation; cancer risk; controlled study; Epstein Barr virus; genotype environment interaction; high risk population; human; human experiment; infection risk; microarray analysis; nonhuman; normal human; priority journal; protein targeting; proteomics; serodiagnosis; smoking; Taiwan; virus reactivation; virus strain; Epstein Barr virus; Epstein Barr virus infection; immunology; individuality; male; protein transport; Antibodies, Viral; Antigens, Viral; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunoglobulin A; Immunoglobulin G; Individuality; Male; Protein Transport; Proteome; Taiwan
Publisher
Oxford University Press
Type
journal article