Epstein-Barr virus -specific Functional Antibody Signatures in the Context of Nasopharyngeal Carcinoma Development

Nasopharyngeal carcinoma is linked to Epstein-Barr virus infection in endemic areas. Using Systems Serology, we assessed antibody subclass, isotype, and Fc-gamma receptor (FcγR) binding, along with Fc-effector functions in NPC patients, matched controls, and multiplex family members from Taiwan, plus NPC patients from Singapore with survival data. NPC patients showed expanded responses, especially neutrophil phagocytosis and complement deposition. Before NPC onset, individuals had elevated EBV-specific IgM levels suggesting an early response to viral activity. Controls exhibited increased IgG2 levels and FcγRIIB binding, suggesting lower inflammatory responses. Efficient antibody-dependent activation of NK cells and monocyte phagocytosis were also observed in controls. We identified a multivariate antibody signature linked to survival after treatment. Our study points to novel biomarkers that may guide NPC clinical management and therapeutics.