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From the Service of Neurology (L.S., A.S., F.G.), Hospital Clinic, Universitat de Barcelona, and Institut d’ Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Neurology (M.T., J.V.), Leiden University Medical Center, the Netherlands; and Molecular Biology and Genetics Department (A.O.G.), Bilkent University, Ankara, Turkey.
* To whom correspondence should be addressed. E-mail: fgraus{at}clinic.ub.es.
ABSTRACT
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.
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  M. J. Titulaer, R. Klooster, M. Potman, L. Sabater, F. Graus, I. M. Hegeman, P. E. Thijssen, P. W. Wirtz, A. Twijnstra, P. A.E. S. Smitt, et al. SOX Antibodies in Small-Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome: Frequency and Relation With Survival J. Clin. Oncol., September 10, 2009; 27(26): 4260 - 4267. [Abstract] [Full Text] [PDF]
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