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

• Published in: Neurology Vol. 50; no. 2; p. 475
• Main Authors: Verschuuren, J J, Dalmau, J, Tunkel, R, Lang, B, Graus, F, Schramm, L, Posner, J B, Newsom-Davis, J, Rosenfeld, M R
• Format: Journal Article
• Language: English
• Published: United States 01.02.1998
• Subjects: 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
• ISSN: 0028-3878
• 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.