GABAB receptor antibodies in limbic encephalitis and anti-GAD–associated neurologic disorders
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Abstract
Background: γ-Aminobutyric acid-B receptor antibodies (GABABR-ab) were recently described in 15 patients with limbic encephalitis (LE), associated with small-cell lung cancer (SCLC) or with concurrent glutamic acid decarboxylase (GAD) antibodies. We analyzed the frequency of GABABR-ab in 147 patients with LE or neurologic syndromes associated with GAD-ab.
Methods: We examined the presence of GABABR-ab in 70 patients with LE (33 paraneoplastic with onconeural antibodies, 18 paraneoplastic without onconeural antibodies [5 with Gad-ab], and 19 idiopathic with either GAD-ab [5 patients] or seronegative) and 77 patients with GAD-ab-associated neurologic syndromes other than LE (29 stiff-person syndrome, 28 cerebellar ataxia, 14 epilepsy, and 6 with diverse paraneoplastic neurologic syndromes). GABABR-ab were analyzed in serum or CSF by indirect immunofluorescence on HEK293 cells transfected with GABAB1 and GABAB2 receptor subunits.
Results: GABABR-ab were detected in 10 of the 70 patients with LE (14%). Eight had SCLC and 2 were idiopathic. One of the 8 patients with LE with SCLC had an additional onconeural antibody (Hu) and 2 GAD-ab. GABABR-ab were identified in 7 (70%) of the 10 patients with LE and SCLC without onconeural antibodies. GABABR-ab antibodies were not found in patients with GAD-ab and stiff-person syndrome, idiopathic cerebellar ataxia, or epilepsy. However, one patient with GAD-ab, paraneoplastic cerebellar ataxia, and anaplastic carcinoid of the thymus also presented GABABR-ab.
Conclusions: GABABR-ab are the most common antibodies found in LE associated with SCLC previously considered “seronegative.” In patients with GAD-ab, the frequency of GABABR-ab is low and only observed in the context of cancer.
Footnotes
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Study funding: Supported in part by grant PS09/0193 Fondo de Investigaciones Sanitarias, Madrid, Spain (F.G.), and National Cancer Institute/National Institute of Health, RO1CA89054 (J.D.).
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- AMPAR
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- BRSK
- brain serine/threonine kinase
- GABABR-ab
- γ-aminobutyric acid-B receptor antibodies
- GAD
- glutamic acid decarboxylase
- LE
- limbic encephalitis
- LGI1
- leucine-rich, glioma-inactivated 1
- NMDAR
- N-methyl-d-aspartate receptor
- PCD
- paraneoplastic cerebellar degeneration
- SCLC
- small-cell lung cancer
- SPS
- stiff-person syndrome
- VGKC
- voltage-gated potassium channel.
- Received August 18, 2010.
- Accepted November 12, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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