The goal of this study is to determine whether patients with
paraneoplastic cerebellar degeneration (PCD) and
small-cell lung cancer (SCLC) have a specific repertoire of
antibodies, if SOX1
antibodies (SOX1-ab) can predict the presence of SCLC, and if
antibodies to
cell surface antigens occur in this syndrome. Antibody analysis was done using immunohistochemistry on rat brain, immunoblot with recombinant
antigens, screening of
cDNA expression libraries, and immunolabeling of live neurons in 39 patients with PCD and SCLC. VGCC-ab were measured by RIA, and SOX1-ab, Hu-ab, and ZIC4-ab by immunoblot. Lambert-Eaton myastenic syndrome (LEMS) was present in 10 of 23 patients with electrophysiological studies. At least one antibody was detected in 72% of patients. The individual frequencies were: 49% SOX1-ab, 44% VGCC-ab, 31% Hu-ab, and 13% ZIC4-ab. SOX1-ab occurred in 76% of patients with VGCC-ab and 27% of those without VGCC-ab (p = 0.0036). SOX1-ab were not found in 39 patients with sporadic
late-onset cerebellar ataxia, 23 with
cerebellar ataxia and
glutamic acid decarboxylase antibodies, and 73 with PCD and
cancer types other than SCLC (31 without onconeural
antibodies, 25 with Yo-ab , 17 with Tr-ab). Five patients (13%) had
antibodies against unknown neuronal
cell surface antigens but none of them improved with
immunotherapy. One serum immunoreacted against the axon initial segment of neurons and another serum against ELKS1, a
protein highly expressed in the cerebellum that interacts with the beta4-subunit of the VGCC. In conclusion, 72% of patients with PCD and SCLC had one or more
antibodies that indicate the presence of this
tumor. In these patients, VGCC-ab and SOX1-ab occur tightly associated. SOX1-ab are predictors of SCLC in
ataxia patients with a specificity of 100% and sensitivity of 49%. Unlike
limbic encephalitis with SCLC,
antibodies to
cell surface antigens other than VGCC-ab, are infrequent and do not predict response to treatment.