ANTIBODIES AGAINST THE CALCIUM-CHANNEL BETA-SUBUNIT IN LAMBERT-EATON MYASTHENIC SYNDROME

The sera of patients with Lambert-Eaton myasthenic syndrome (LEMS) con tain autoantibodies against several extracellular and intracellular co mponents of the voltage-gated calcium channel (VGCC)/synaptic vesicle release complex. An example of the latter are anti-beta-subunit antibo dies (anti-MysB antibodies). We constructed a full-length cDNA clone o f a human VGCC beta-subunit to produce purified beta-subunit fusion pr otein (MysB protein). Using this protein, we demonstrated that anti-be ta-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 witho ut LEMS. The presence of anti-beta-subunit antibodies was closely asso ciated with high titers of P/Q- and N-type VGCC antibodies. Immunizati on 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 chan nel 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.