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

Lancet neurology, 2010, Vol.9 (1), p.67-76 [Peer Reviewed Journal]

Elsevier Ltd ;ISSN: 1474-4422 ;EISSN: 1474-4465 ;DOI: 10.1016/S1474-4422(09)70324-2 ;PMID: 19962348

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  • Title:
    Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen
  • Author: Lancaster, Eric, MD ; Lai, Meizan, MD ; Peng, Xiaoyu, BS ; Hughes, Ethan, PhD ; Constantinescu, Radu, MD ; Raizer, Jeffrey, MD ; Friedman, Daniel, MD ; Skeen, Mark B, MD ; Grisold, Wolfgang, MD ; Kimura, Akio, MD ; Ohta, Kouichi, MD ; Iizuka, Takahiro, MD ; Guzman, Miguel, MD ; Graus, Francesc, MD ; Moss, Stephen J, PhD ; Balice-Gordon, Rita, PhD ; Dalmau, Josep, MD
  • Subjects: Neurology
  • Is Part Of: Lancet neurology, 2010, Vol.9 (1), p.67-76
  • Description: Summary 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.
  • Language: English
  • Identifier: ISSN: 1474-4422
    EISSN: 1474-4465
    DOI: 10.1016/S1474-4422(09)70324-2
    PMID: 19962348
  • Source: ProQuest One Psychology
    AUTh Library subscriptions: ProQuest Central
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