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

From the Department of Neurology (Dr. Verschuuren), Leiden University Hospital, Leiden, The Netherlands; the Department of Neurology and the Cotzias Laboratory of Neuro-Oncology (Drs. Dalmau, Tunkel, Posner, Rosenfeld, and Schramm), Memorial Sloan-Kettering Cancer Center, New York, Ny; the University Department of Clinical Neurology (Drs. Lang and Newsom-Davis), Institute of Molecular Medicine, Oxford, UK, and the Service of Neurology (Dr. Gram), Hospital Clinic de Barcelona, Barcelona, Spain.

Address correspondence and reprint requests to Dr. Myrna R. Rosenfeld, Department of Neuroiogy, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

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-β-subunit antibodies (anti-MysB antibodies). We constructed a full-length cDNA clone of a human VGCC β-subunit to produce purified β-subunit fusion protein (MysB protein). Using this protein, we demonstrated that anti-β-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-β-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-β-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.

Received June 26, 1997. Accepted in final form September 9, 1997.

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