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

Author

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, Neurology, Immunology, Biochemistry, Sub Cell Biology, and Celbiologie

Subjects
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
Abstract

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.

Published
2019
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4. Pediatric autoimmune encephalitis: Recognition and diagnosis

Author

de Bruijn, Marienke, Bruijstens, Arlette, Bastiaansen, Danielle, Sonderen, Agnes, Schreurs, Marco, Sillevis Smitt, Peter, Hintzen, Rogier, Neuteboom, Rinze, Titulaer, Maarten, de Bruijn, Marienke, Bruijstens, Arlette, Bastiaansen, Danielle, Sonderen, Agnes, Schreurs, Marco, Sillevis Smitt, Peter, Hintzen, Rogier, Neuteboom, Rinze, and Titulaer, Maarten

Published
2020

5. Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

Author

Bastiaansen, Danielle, Timmermans, Mieke, Smid, Marcel, van Deurzen, Carolien, Hulsenboom, Esther, Prager - van der Smissen, Wendy, Foekens, Renée, Trapman - Jansen, Anita, Sillevis Smitt, Peter, Luider, Theo, Martens, John, van Duijn, Martijn, Bastiaansen, Danielle, Timmermans, Mieke, Smid, Marcel, van Deurzen, Carolien, Hulsenboom, Esther, Prager - van der Smissen, Wendy, Foekens, Renée, Trapman - Jansen, Anita, Sillevis Smitt, Peter, Luider, Theo, Martens, John, and van Duijn, Martijn

Published
2020

6. The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies

Author

Sub Cell Biology, Celbiologie, 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, 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, and Titulaer, Maarten J

Published
2019

7. Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis

Author

De Jong - de Bruijn, Marjolein, Sonderen, Agnes, Hameete, Marleen, Bastiaansen, Danielle, Schreurs, Marco, Rouhl, RPW, van Donselaar, CA, Majoie, M, Neuteboom, Rinze, Sillevis Smitt, Peter, Thijs, RD, Titulaer, Maarten, De Jong - de Bruijn, Marjolein, Sonderen, Agnes, Hameete, Marleen, Bastiaansen, Danielle, Schreurs, Marco, Rouhl, RPW, van Donselaar, CA, Majoie, M, Neuteboom, Rinze, Sillevis Smitt, Peter, Thijs, RD, and Titulaer, Maarten

Published
2019

8. Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis

Author

de Bruijn, Marienke, Aarsen, Femke, van Oosterhout, MP, van der Knoop, Marieke, Catsman - Berrevoets, Coriene, Schreurs, Marco, Bastiaansen, Danielle, Sillevis Smitt, Peter, Neuteboom, Rinze, Titulaer, Maarten, de Bruijn, Marienke, Aarsen, Femke, van Oosterhout, MP, van der Knoop, Marieke, Catsman - Berrevoets, Coriene, Schreurs, Marco, Bastiaansen, Danielle, Sillevis Smitt, Peter, Neuteboom, Rinze, and Titulaer, Maarten

Published
2018

9. The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies.

Author

Coevorden-Hameete, Marleen H van, Bruijn, Marienke A A M de, Graaff, Esther de, 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, Smitt, Peter A E Sillevis, Titulaer, Maarten J, van Coevorden-Hameete, Marleen H, de Bruijn, Marienke A A M, de Graaff, Esther, and Sillevis Smitt, Peter A E

Subjects
ENCEPHALITIS, GABA, ANTI-NMDA receptor encephalitis, AUTOANTIBODIES, GABA receptors, SMALL cell carcinoma, MASS analysis (Spectrometry)
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
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