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

Author

Listed:
  • Laurent Martin

    (The University of Arizona
    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
    Saint Louis University)

  • Shizhen Luo

    (The University of Arizona)

  • Frank Porreca

    (The University of Arizona)

  • Mohab Ibrahim

    (The University of Arizona
    The University of Arizona)

  • Véronique Rogemond

    (Université Claude Bernard Lyon 1)

  • Jérôme Honnorat

    (Université Claude Bernard Lyon 1)

  • Rajesh Khanna

    (The University of Arizona
    University of Florida)

  • Aubin Moutal

    (The University of Arizona
    Saint Louis University)

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.

Suggested Citation

  • 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 & Sh, 2025. "Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62380-y
    DOI: 10.1038/s41467-025-62380-y
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