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

[[abstract]]Background: Little is known about variation in antibody response targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk. Methods: We utilized a microarray to measure IgG and IgA antibody responses against 199 EBV protein sequences from five EBV strains in 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the association between environmental and genetic risk factors and variation in antibody responses. Results: Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median IgG vs. IgA positivity rate: 46.5% vs. 17.3%, Prank-test = 1.6 x 10-46). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across class. The mucosal exposure (IgA response) to proteins involved in EBV reactivation was associated with smoking (PSKAT-C= 0.002), 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 response 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 identifying targets for effective immunodiagnostics