Article Dans Une Revue Journal of Neuroimmunology Année : 2024

Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain

Laurent Martin
  • Fonction : Auteur
Harrison Stratton
  • Fonction : Auteur
Kimberly Gomez
  • Fonction : Auteur
Le Duy Do
  • Fonction : Auteur
Santiago Loya-Lopez
  • Fonction : Auteur
Cheng Tang
  • Fonction : Auteur
Aida Calderon-Rivera
  • Fonction : Auteur
Dongzhi Ran
  • Fonction : Auteur
Venkatrao Nunna
  • Fonction : Auteur
Shreya Bellampalli
  • Fonction : Auteur
Liberty François-Moutal
  • Fonction : Auteur
Nicolas Dumaire
  • Fonction : Auteur
Lyuba Salih
  • Fonction : Auteur
Shizhen Luo
  • Fonction : Auteur
Frank Porreca
  • Fonction : Auteur
Mohab Ibrahim
  • Fonction : Auteur
Véronique Rogemond
  • Fonction : Auteur
Rajesh Khanna
  • Fonction : Auteur
Aubin Moutal
  • Fonction : Auteur

Résumé

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. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.

Dates et versions

hal-04991934 , version 1 (14-03-2025)

Identifiants

Citer

Laurent Martin, Harrison Stratton, Kimberly Gomez, Le Duy Do, Santiago Loya-Lopez, et al.. Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain. Journal of Neuroimmunology, 2024, 390, pp.578346. ⟨10.1101/2024.05.04.592533⟩. ⟨hal-04991934⟩
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