BACKGROUND/OBJECTIVE: We reported that 43% of patients with Lambert-Eaton 
myasthenic syndrome (LEMS) and small cell lung cancer (SCLC) had an antibody 
called anti-glial nuclear antibody (AGNA), defined by the immunoreaction with 
the nuclei of the Bergmann glia of the cerebellum. This study was undertaken to 
identify the antigen recognized by AGNA and to confirm the association with 
paraneoplastic LEMS in a larger series.
METHODS: We probed a fetal brain cDNA library with AGNA-positive sera. The 
presence of antibodies against the isolated antigen was detected by immunoblot 
of phage plaques from two positive clones. We studied 105 patients with LEMS (55 
with SCLC), 50 with paraneoplastic neurologic syndromes, SCLC, and Hu 
antibodies, and 50 with only SCLC.
RESULTS: Probing of the fetal brain expression library with AGNA sera resulted 
in the isolation of SOX1, a highly immunogenic tumor antigen in SCLC. IgG eluted 
from SOX1 clones produced the same cerebellar immunoreactivity as of AGNA sera. 
SOX1 antibodies were present in 64% of patients with LEMS and SCLC but in none 
of the 50 with idiopathic LEMS (p < 0.0001). Compared with paraneoplastic LEMS, 
the frequency of SOX1 antibodies was significantly lower in patients with Hu 
antibodies (32%, p = 0.002) and in those with only SCLC (22%).
CONCLUSIONS: SOX1 is the antigen recognized by anti-glial nuclear 
antibody-positive sera. The detection of SOX1 antibodies in patients with 
Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell 
lung cancer and may be used to follow more closely those LEMS patients with no 
evidence of cancer at the initial workup.