The expanded clinical spectrum of anti-GABA(B)R encephalitis and added value of KCTD16 autoantibodies

In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABA(B)R) antibodies, identify additional autoantibodies in patients with anti-GABA(B)R encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods...

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Detalles Bibliográficos
Autores principales: van Coevorden-Hameete, Marleen H, de Bruijn, Marienke A A M, de Graaff, Esther, Bastiaansen, Danielle A E M, Schreurs, Marco W J, Demmers, Jeroen A A, Ramberger, Melanie, Hulsenboom, Esther S P, Nagtzaam, Mariska M P, Boukhrissi, Sanae, Veldink, Jan H, Verschuuren, Jan J G M, Hoogenraad, Casper C, Sillevis Smitt, Peter A E, Titulaer, Maarten J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Original Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536844/
https://www.ncbi.nlm.nih.gov/pubmed/31009048
http://dx.doi.org/10.1093/brain/awz094
Descripción
Sumario:In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABA(B)R) antibodies, identify additional autoantibodies in patients with anti-GABA(B)R encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods for the detection of GABA(B)R antibodies. Patients (n = 3225) were tested for the presence of GABA(B)R antibodies using cell-based assay, immunohistochemistry and live hippocampal neurons. Clinical data were obtained retrospectively. Potassium channel tetramerization domain-containing (KCTD)16 antibodies were identified by immunoprecipitation, mass spectrometry analysis and cell-based assays. KCTD16 antibodies were identified in 23/32 patients with anti-GABA(B)R encephalitis, and in 1/26 patients with small cell lung carcinoma and Hu antibodies, but not in 329 healthy subjects and disease controls. Of the anti-GABA(B)R encephalitis patients that were screened sufficiently, 18/19 (95%) patients with KCTD16 antibodies had a tumour versus 3/9 (33%) anti-GABA(B)R encephalitis patients without KCTD16 antibodies (P = 0.001). In most cases this was a small cell lung carcinoma. Patients had cognitive or behavioural changes (97%) and prominent seizures (90%). Thirteen patients developed a refractory status epilepticus with intensive care unit admittance (42%). Strikingly, 4/32 patients had a rapidly progressive dementia. The addition of KCTD16 to the GABA(B)R cell-based assay improved sensitivity of the in-house fixed cell-based assay, without loss of specificity. Twenty-two of 26 patients improved (partially) to immunotherapy or chemotherapy. Anti-GABA(B)R encephalitis is a limbic encephalitis with prominent, severe seizures, but patients can also present with rapidly progressive dementia. The co-occurrence of KCTD16 antibodies points towards a paraneoplastic origin. The addition of KCTD16 improves the sensitivity of the cell-based assay.

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