Abstract
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.
Data availability
All data are available upon reasonable request to the corresponding author (clinical data) and Kaia Palm (MVA-data, [kaia@protobios.com](mailto: kaia@protobios.com)).
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Acknowledgements
The authors would like to thank the research nurse Eija Ruoppa for her excellent work. We thank all patients who participated in this study. Protobios acknowledges the excellent technical support from its team members Alex Sirp, Maria Piirsalu, Regina Maruste, Loviisa Pihlas, Epp Väli, and Helen Ausman. The authors thank Les Hearn, MSc, for reviewing the English language of the manuscript.
Funding
This study was supported by a grant to Protobios from the EU’s HE research and innovation program under grant agreement No 101095436, with the clause that “Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the granting authority can be held responsible for them”. In addition, the research by Protobios was supported by funding from the Estonian Ministry of Education and Research (5.1-4/20/170) and Estonian Research Council (PRG1953, KP and PSG691, MT). The clinical part of the study at the Helsinki University Hospital was supported by European Union FP7 (#Health_F2_2013-602891) grant NeuroPain and the Helsinki University Hospital Research Funds to the Department of Anaesthesiology, Intensive Care and Pain Medicine (Y102011092).
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EK, KP, HH, HS, AR and PJT contributed to the study design. EK and HH contributed to the data collection. HH conducted the clinical examination of the patients. HS, AR, MU, MT and AP performed immunoproliferation and validation experiments. HS, AR, MU, AP, MT, JN, LM and KP contributed to the data analysis and making of the figures and tables. HS, KP, AR and LM wrote the first draft of the manuscript. All authors were involved in the data interpretation, review and approval of the final version of the manuscript.
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Sadam, H., Mustonen, L., Rähni, A. et al. Comprehensive antigen profiling predicts post-surgical neuropathic pain in women treated for breast cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41637-6
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DOI: https://doi.org/10.1038/s41598-026-41637-6
