The expanded clinical spectrum of anti-GABA(B)R encephalitis and added value of KCTD16 autoantibodies
| Autor: | 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, Sub Cell Biology, Celbiologie |
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| Přispěvatelé: | Neurology, Immunology, Biochemistry, Sub Cell Biology, Celbiologie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty medicine.medical_treatment Neuronal Surface Antigens Nerve Tissue Proteins Status epilepticus 03 medical and health sciences Status Epilepticus 0302 clinical medicine Seizures medicine Humans Immunologic Factors gamma-Aminobutyric Acid Aged Autoantibodies Aged 80 and over Neurons Autoimmune encephalitis biology business.industry Limbic encephalitis Intracellular Signaling Peptides and Proteins Autoantibody Original Articles Immunotherapy Middle Aged medicine.disease autoimmune encephalitis paraneoplastic neurological disorders 030104 developmental biology antineuronal autoantibodies neuronal surface antigens biology.protein Encephalitis Immunohistochemistry Female Neurology (clinical) medicine.symptom Antibody business 030217 neurology & neurosurgery |
| Zdroj: | Brain, 142, 1631-1643 Brain, 142, 1631-1643. Oxford University Press Brain, 142(6), 1631. Oxford University Press Brain |
| ISSN: | 0006-8950 |
| DOI: | 10.1093/brain/awz094 |
| Popis: | Many patients with anti-GABABR encephalitis respond to immunotherapy, emphasizing the importance of early diagnosis. Van Coevorden-Hameete et al. show that while the majority of patients have epilepsy, others present with progressive dementia without seizures. Adding KCTD16, an auxiliary protein, to a GABABR cell-based assay improves sensitivity without loss of specificity. In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABABR) antibodies, identify additional autoantibodies in patients with anti-GABABR encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods for the detection of GABABR antibodies. Patients (n = 3225) were tested for the presence of GABABR 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-GABABR 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-GABABR encephalitis patients that were screened sufficiently, 18/19 (95%) patients with KCTD16 antibodies had a tumour versus 3/9 (33%) anti-GABABR 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 GABABR 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-GABABR 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. |
| Databáze: | OpenAIRE |
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