Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen

Eric Lancaster, Meizan Lai, Xiaoyu Peng, Ethan Hughes, Radu Constantinescu, Jeffrey Raizer, Daniel Friedman, Mark B. Skeen, Wolfgang Grisold, Akio Kimura, Kouichi Ohta, Takahiro Iizuka, Miguel Guzman, Francesc Graus, Stephen J. Moss, Rita Balice-Gordon, Josep Dalmau*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

602 Scopus citations

Abstract

Background: Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. Methods: 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABAB1 or GABAB2 receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. Findings: All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABAB receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABAB receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0·005). Low levels of GABAB1 receptor antibodies were identified in two of 104 controls (p<0·0001). Interpretation: GABAB receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. Funding: National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalThe Lancet Neurology
Volume9
Issue number1
DOIs
StatePublished - Jan 2010

ASJC Scopus subject areas

  • Clinical Neurology

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