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.