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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 70, Number 12, March 18, 2008 Data Supplement All Versions of this Article: 01.wnl.0000281663.81079.24v1 70/12/924    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sabater, L. Articles by Graus, F. Search for Related Content PubMed PubMed Citation Articles by Sabater, L. Articles by Graus, F.

SOX1 antibodies are markers of paraneoplastic Lambert–Eaton myasthenic syndrome

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.

Address correspondence and reprint requests to Dr. F. Graus, Servei de Neurologia, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain fgraus{at}clinic.ub.es

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.

Abbreviations: AGNA = anti-glial nuclear antibody; LEMS = Lambert–Eaton myasthenic syndrome; SCLC = small cell lung cancer; VGCC = voltage-gated calcium channel; VGKC = voltage-gated potassium channel.

Supplemental data at www.neurology.org

Editorial, page 906

e-Pub ahead of print on November 21, 2007, at www.neurology.org.

Supported in part by grants QLG1-CT-2002-01756 of the European Union, PI030028 Fondo de Investigaciones Sanitarias, Madrid, Spain, and the Prinses Beatrix Fonds, the Netherlands.

Disclosure: The authors report no conflicts of interest.

Received April 25, 2007. Accepted in final form July 6, 2007.

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