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Antibodies to synthetic peptides of the alA subunit of the voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome

From the Department of Neurology, Kanazawa University School of Medicine, Kanazawa, Japan.

To search for antigenic sites in the molecular structure of alA subunit of the voltage-gated calcium channel (VGCC) (P/Q-type) in the Lambert-Eaton myasthenic syndrome (LEMS), we studied by immunoprecipitation assay serum samples from 30 LEMS patients (16 with small cell lung carcinoma (SCLC), 20 disease controls (10 with SCLC without LEMS and 10 with myasthenia gravis), and 15 healthy controls. Synthetic peptide antigens corresponded to the extracellular region (S5-S6 linker region) of each of the four domains forming the al subunit of P/Q-type VGCC. In addition, we studied serum samples for anti-P/Q-type VGCC antibodies by using w-conotoxin MVIIC-labeled extract of human cerebellum as an antigen. Among sera of 30 LEMS patients, nine samples (30%) (six with SCLC) were positive for antibodies to the domain IV S5-S6 linker peptide, and six samples (20%) (five with SCLC) were positive for antibodies to the domain II S5-S6 linker peptide. Only two of 15 antipeptide-positive sera were positive for both antibodies. Titers for antibodies to domain IV, as well as those for antibodies to domain II, correlated with those of anti-P/Q-type VGCC (human cerebellum extract) antibodies. The antipeptide antibody was present in only one of 20 disease controls, a patient with SCLC without LEMS. Our observations suggest two potential epitopes of LEMS antibodies.

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				K. Iwasa, M. Takamori, K. Komai, and Y. Mori Recombinant calcium channel is recognized by Lambert-Eaton myasthenic syndrome antibodies Neurology, February 8, 2000; 54(3): 757 - 757. [Abstract] [Full Text] [PDF]

				K. L. Engisch, M. M. Rich, N. Cook, and M. C. Nowycky Lambert-Eaton Antibodies Inhibit Ca2+ Currents But Paradoxically Increase Exocytosis during Stimulus Trains in Bovine Adrenal Chromaffin Cells J. Neurosci., May 1, 1999; 19(9): 3384 - 3395. [Abstract] [Full Text] [PDF]