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      SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome

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      Author
      Sabater, L.
      Titulaer, M.
      Saiz, A.
      Verschuuren, J.
      Güre, A. O.
      Graus, F.
      Date
      2008
      Source Title
      Neurology
      Print ISSN
      0028-3878
      Publisher
      Lippincott Williams & Wilkins
      Volume
      70
      Issue
      12
      Pages
      924 - 928
      Language
      English
      Type
      Article
      Item Usage Stats
      140
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      204
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      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.
      Keywords
      Antinuclear antibody
      Glial nuclear antibody
      Hu antibody
      Transcription factor Sox1
      Tumor antigen
      Unclassified drug
      Antigen detection
      Article
      Controlled study
      DNA library
      Eaton lambert syndrome
      Female
      Gene deletion
      Human
      Human tissue
      Immunoblotting
      Immunoreactivity
      Lung small cell cancer
      Major clinical study
      Nucleotide sequence
      Priority journal
      Aged
      Animals
      Antigens, Neoplasm
      Autoantibodies
      Biological markers
      Calcium channels
      Carcinoma, small cell
      Cerebellum
      DNA-Binding Proteins
      Female
      High Mobility Group Proteins
      Humans
      Immunoblotting
      Lambert-Eaton myasthenic syndrome
      Lung neoplasms
      Male
      Neuroglia
      Paraneoplastic syndromes
      Predictive value of tests
      Prognosis
      Rats
      Tumor markers, biological
      Permalink
      http://hdl.handle.net/11693/23183
      Published Version (Please cite this version)
      http://dx.doi.org/10.1212/01.wnl.0000281663.81079.24
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