SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome
Author
Sabater, L.
Titulaer, M.
Saiz, A.
Verschuuren, J.
Güre, A. O.
Graus, F.
Date
2008Source Title
Neurology
Print ISSN
0028-3878
Publisher
Lippincott Williams & Wilkins
Volume
70
Issue
12
Pages
924 - 928
Language
English
Type
ArticleItem Usage Stats
140
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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 antibodyGlial 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