INCIDENCE OF SERUM ANTI-P Q-TYPE AND ANTI-N-TYPE CALCIUM-CHANNEL AUTOANTIBODIES IN THE LAMBERT-EATON MYASTHENIC SYNDROME/

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which autoantibodies are directed against voltage-gated calcium cha nnels (VGCCs) at presynaptic nerve terminals. We first demonstrated th e presence of P/Q-type and N-type VGCCs in digitonin extracts prepared from human and rabbit cerebellum using the specific ligands I-125-ome ga-conotoxin MVIIC (I-125-omega-CmTx) and I-125-omega-conotoxin GVIA ( I-125-omega-CgTx), respectively. We then tested sera from 72 LEMS pati ents' 25 with proven small cell lung cancer (SCLC) and 66 healthy or o ther neurological, SCLC or autoimmune disease controls in an immunopre cipitation assay using I-125-omega-CmTx-labelled (P/Q-type) VGCCs in h uman cerebellar extract. Sixty-six of 72 LEMS serum samples (91.7%) we re positive for the presence of VGCC antibodies, as defined as a titre greater than 3 standard deviations above the mean for the healthy con trols (n=22). Rabbit cerebellar extract as antigen gave similar result s (r=0.94, P<0.001, n=30). By contrast, only 24/72 (33%) LEMS sera wer e positive in the assay for anti-N-type VGCC antibodies using I-125-om ega-CgTx. All these 24 were also positive in the I-125-omega-CmTx assa y. All healthy and disease control sera were negative in both assays. The anti-P/Q-type VGCC antibody titres did not correlate with an elect rophysiological index of disease severity across individuals; however, longitudinal studies in a LEMS patient with SCLC receiving chemothera py, and in a non-SCLC LEMS patient receiving immunosuppressive therapy showed an inverse relation between antibody titre and disease severit y. These results support the view that anti-P/Q-type VGCC antibodies a re implicated in the motor disorder in LEMS, and show that the omega-C mTx radioimmunoassay is a highly specific and sensitive means of detec ting them. (C) 1997 Elsevier Science B.V.