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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月7日

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  • 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,
  • Aubin Moutal

摘要

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.