Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats

Laurent Martin, Harrison J. Stratton, Lyuba Y. Salih, Nicolas LA. Dumaire, Kimberly Gomez, Le Duy Do, Santiago Loya-Lopez, Cheng Tang, Aida Calderon-Rivera, Dongzhi Ran, Venkatrao Nunna, Shreya S. Bellampalli, Liberty François-Moutal, Shizhen Luo, Frank Porreca, Mohab Ibrahim, Véronique Rogemond, Jérôme Honnorat, Rajesh Khanna and Aubin Moutal ()
Additional contact information
Laurent Martin: The University of Arizona
Harrison J. Stratton: The University of Arizona
Lyuba Y. Salih: Saint Louis University
Nicolas LA. Dumaire: Saint Louis University
Kimberly Gomez: The University of Arizona
Le Duy Do: Université Claude Bernard Lyon 1
Santiago Loya-Lopez: The University of Arizona
Cheng Tang: The University of Arizona
Aida Calderon-Rivera: The University of Arizona
Dongzhi Ran: The University of Arizona
Venkatrao Nunna: Saint Louis University
Shreya S. Bellampalli: The University of Arizona
Liberty François-Moutal: The University of Arizona
Shizhen Luo: The University of Arizona
Frank Porreca: The University of Arizona
Mohab Ibrahim: The University of Arizona
Véronique Rogemond: Université Claude Bernard Lyon 1
Jérôme Honnorat: Université Claude Bernard Lyon 1
Rajesh Khanna: The University of Arizona
Aubin Moutal: The University of Arizona

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen, with approximately 80% of these patients experiencing painful neuropathies. Here we investigate the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain and find that patient-derived CV2/CRMP5-Abs bind to their target on rat dorsal root ganglia (DRG) and superficial laminae of the spinal cord, to induce DRG neuron hyperexcitability and mechanical hypersensitivity. These effects from patient-derived Abs are recapitulated in rats immunized with a DNA vaccine for CRMP5, in which therapeutic treatment with anti-CD20 depleting B cells ameliorates autoimmunity and neuropathy. Our data thus reveal a mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes and implicates CV2/CRMP5-Abs as a potential target for treating paraneoplastic neurological syndromes.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62380-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62380-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62380-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().