Comprehensive antigen profiling predicts post-surgical neuropathic pain in women treated for breast cancer

The importance of neuroimmune interactions in neuropathic pain (NP) has been established, but antibody-mediated mechanisms remain underexplored. In this explorative case-control study, we analyzed antibody profiles in patients with intercostobrachial nerve injury during breast cancer (BC) surgery. We compared 27 patients who developed chronic NP with 30 who remained NP-free, despite similar nerve injury. Plasma samples were collected before surgery and 4–9 years later. Mimotope variation analysis (MVA), a next generation random peptide phage display method revealed highly individual yet shared antigen profiles. We identified 1882 antibody epitopes differing between the study groups and that were associated with 79 common human pathogens. NP patients showed elevated pre-surgical antibody responses to viral epitopes of CMV (cytomegalovirus), EBV (Epstein-Barr virus), human papilloma virus-16 (HPV-16), human rhinovirus C3 (HRV C3), Herpes Simplex-1 (HSV-1), Herpes Simplex-2 (HSV-2), while antibody levels against Coxsackievirus B3 (CVB3) were lower. These findings persisted over time. The combination of responses to five viral epitopes (CVB3, EBV, CMV, HPV-16, HSV-2) predicted persistent NP (AUC 0.9, 95% CI 0.794–0.963). These findings implicate elevated antiviral immune responses in NP pathogenesis and encourage further clinical and basic research on the molecular mechanisms and novel treatment strategies for managing NP.