Antibodies against the calcium channel beta-subunit in Lambert-Eaton myasthenic syndrome

Neurology. 1998 Feb;50(2):475-9. doi: 10.1212/wnl.50.2.475.


The sera of patients with Lambert-Eaton myasthenic syndrome (LEMS) contain autoantibodies against several extracellular and intracellular components of the voltage-gated calcium channel (VGCC)/synaptic vesicle release complex. An example of the latter are anti-beta-subunit antibodies (anti-MysB antibodies). We constructed a full-length cDNA clone of a human VGCC beta-subunit to produce purified beta-subunit fusion protein (MysB protein). Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS. The presence of anti-beta-subunit antibodies was closely associated with high titers of P/Q- and N-type VGCC antibodies. Immunization of rats with the purified MysB protein induced high antibody titers, but no signs of neurologic dysfunction were found. We conclude that anti-beta-subunit antibodies are not likely to interfere with ion channel function, but their presence could explain the cross-reactivity of LEMS sera with several subtypes of VGCCs and the lack of correlation between anti-VGCC antibody titer and clinical severity of disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / blood*
  • Blood Donors
  • Calcium Channels / analysis
  • Calcium Channels / immunology*
  • Calcium Channels / metabolism
  • Calcium Channels, L-Type
  • Cell Membrane / metabolism
  • Cerebellum / metabolism
  • Cerebral Cortex / metabolism
  • Cloning, Molecular
  • Electrophysiology
  • Female
  • Humans
  • Lambert-Eaton Myasthenic Syndrome / diagnosis
  • Lambert-Eaton Myasthenic Syndrome / immunology*
  • Lambert-Eaton Myasthenic Syndrome / physiopathology
  • Macromolecular Substances
  • Nerve Tissue Proteins / immunology*
  • Rats
  • Rats, Inbred Lew
  • Recombinant Fusion Proteins / immunology
  • Reference Values


  • Autoantibodies
  • CACNA1C protein, human
  • Calcium Channels
  • Calcium Channels, L-Type
  • Macromolecular Substances
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins