Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia

Ann Neurol. 2011 Feb;69(2):303-11. doi: 10.1002/ana.22297.

Abstract

Objective: To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC).

Methods: Clinical analysis was performed on patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity.

Results: Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients' antibodies reacted with brain and peripheral nerve in a pattern that colocalized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients also had myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median, 8 months; range, 6-84 months).

Interpretation: Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important, because it responds to immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antibody Specificity / immunology
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Encephalitis / immunology*
  • Female
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Isaacs Syndrome / immunology*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Peripheral Nerves / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • CNTNAP2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins