Different pain phenotypes are associated with anti-Caspr2 autoantibodies

J Neurol. 2024 May;271(5):2736-2744. doi: 10.1007/s00415-024-12224-4. Epub 2024 Feb 22.

Abstract

Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.

Keywords: Autoantibody; Caspr2; IgG subclass; IgG4; Pain.

MeSH terms

  • Aged
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Cohort Studies
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Membrane Proteins* / immunology
  • Middle Aged
  • Nerve Tissue Proteins* / immunology
  • Pain / blood
  • Pain / etiology
  • Pain / immunology
  • Phenotype*

Substances

  • Autoantibodies
  • CNTNAP2 protein, human
  • Immunoglobulin G
  • Membrane Proteins
  • Nerve Tissue Proteins