PhIP-Seq reveals geography- and disease-associated human herpesvirus antibody repertoires and distinct EBV response modules.

German cohorts show broader EBV antibody reactivity than Malagasy controls, with increased reactivity in primary sclerosing cholangitis, detected by PhIP-Seq across 908 sera.

• Why it matters: EBV is linked to immune-mediated inflammatory diseases, yet herpesvirus antibody repertoires across geography and disease states are not well mapped with multiplex methods.
• What they did: PhIP-Seq profiled antibodies to all nine human herpesviruses in 908 serum samples from 848 individuals in Madagascar and Germany, and proteome-wide EBV reactivity covered 60 of 79 proteins.
• The result: Co-occurrence analyses in German cohorts identified an EBNA2-EBNA3A/B/C module and BFRF3-EBNA1 and BZLF1-BMRF1 pairs, and peptide ELISA confirmed individual-level concordance for EBNA1.