ANTIBODIES TO RECOMBINANT SYNAPTOTAGMIN AND CALCIUM-CHANNEL SUBTYPES IN LAMBERT-EATON MYASTHENIC SYNDROME

Several proteins have been postulated as possible targets of immune at tack in Lambert-Eaton myasthenic syndrome (LEMS). Heterogeneity of aut oantibodies in sera from 20 LEMS patients was studied by comparing the ir reactivity to synaptotagmin, a synaptic vesicle protein, and voltag e-gated calcium channels (VGCCs). Six patients' sera(1 with small cell lung carcinoma (SCLC)) contained antibodies specifically recognizing the recombinant synaptotagmin on immunoblots. Thirteen (11 with SCLC) and 16 (11 with SCLC and 1 with poorly differentiated cell carcinoma i n the lung) patients' sera immunoprecipitated omega-conotoxin GVIA-lab eled N-type and omega-conotoxin MVIIC-labeled Q-type VGCCs, respective ly. Three of 6 synaptoglagmin-positive sera had cross-reactivity with N and/or Q subtypes of VGCC; the remaining 3 showed no cross-reactivit y with VGCCs. Results indicate that LEMS sera are heterogeneous in the spectrum of containing antibodies, and suggest that this heterogeneit y reflects the immune response to various synaptic proteins including not only multiple VGCCs but also synaptosecretory complex proteins.