GABA A receptor autoimmunity: A multicenter experience

Kevin O'Connor, Patrick Waters, Lars Komorowski, Anastasia Zekeridou, Chu Yueh Guo, Victor C. Mgbachi, Christian Probst, Swantje Mindorf, Bianca Teegen, Jeffrey M. Gelfand, Michael D. Geschwind, Vanda A Lennon, Sean J Pittock, Andrew B McKeon

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

ObjectiveWe sought to validate methods for detection and confirmation of GABA A receptor (R)-IgG and clinically characterize seropositive cases.MethodsArchived serum and CSF specimens (185 total) suspected to harbor GABA A R-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABA A R-IgG positivity by IFA, based on prior reports and comparison with commercial GABA A R antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABA A R-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABA A R subunits.ResultsEight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABA A R-IgG positive. Patient IgGs were always reactive with α1β3 GABA A R subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1-71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy.ConclusionsThough not as common as NMDA-R encephalitis, GABA A R encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.

Original languageEnglish (US)
Article numbere552
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume6
Issue number3
DOIs
StatePublished - May 1 2019

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GABA-A Receptors
Autoimmunity
gamma-Aminobutyric Acid
Immunoglobulin G
Encephalitis
Clinical Laboratory Techniques
Validation Studies
HEK293 Cells
N-Methylaspartate
Indirect Fluorescent Antibody Technique
Serum
Anticonvulsants
Immunotherapy
Nervous System
Atrophy
Fluorescent Antibody Technique
Germany
Seizures
Plasmids
Staining and Labeling

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

O'Connor, K., Waters, P., Komorowski, L., Zekeridou, A., Guo, C. Y., Mgbachi, V. C., ... McKeon, A. B. (2019). GABA A receptor autoimmunity: A multicenter experience. Neurology: Neuroimmunology and NeuroInflammation, 6(3), [e552]. https://doi.org/10.1212/NXI.0000000000000552

GABA A receptor autoimmunity : A multicenter experience. / O'Connor, Kevin; Waters, Patrick; Komorowski, Lars; Zekeridou, Anastasia; Guo, Chu Yueh; Mgbachi, Victor C.; Probst, Christian; Mindorf, Swantje; Teegen, Bianca; Gelfand, Jeffrey M.; Geschwind, Michael D.; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew B.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 6, No. 3, e552, 01.05.2019.

Research output: Contribution to journalArticle

O'Connor, K, Waters, P, Komorowski, L, Zekeridou, A, Guo, CY, Mgbachi, VC, Probst, C, Mindorf, S, Teegen, B, Gelfand, JM, Geschwind, MD, Lennon, VA, Pittock, SJ & McKeon, AB 2019, 'GABA A receptor autoimmunity: A multicenter experience', Neurology: Neuroimmunology and NeuroInflammation, vol. 6, no. 3, e552. https://doi.org/10.1212/NXI.0000000000000552
O'Connor K, Waters P, Komorowski L, Zekeridou A, Guo CY, Mgbachi VC et al. GABA A receptor autoimmunity: A multicenter experience. Neurology: Neuroimmunology and NeuroInflammation. 2019 May 1;6(3). e552. https://doi.org/10.1212/NXI.0000000000000552
O'Connor, Kevin ; Waters, Patrick ; Komorowski, Lars ; Zekeridou, Anastasia ; Guo, Chu Yueh ; Mgbachi, Victor C. ; Probst, Christian ; Mindorf, Swantje ; Teegen, Bianca ; Gelfand, Jeffrey M. ; Geschwind, Michael D. ; Lennon, Vanda A ; Pittock, Sean J ; McKeon, Andrew B. / GABA A receptor autoimmunity : A multicenter experience. In: Neurology: Neuroimmunology and NeuroInflammation. 2019 ; Vol. 6, No. 3.
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abstract = "ObjectiveWe sought to validate methods for detection and confirmation of GABA A receptor (R)-IgG and clinically characterize seropositive cases.MethodsArchived serum and CSF specimens (185 total) suspected to harbor GABA A R-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABA A R-IgG positivity by IFA, based on prior reports and comparison with commercial GABA A R antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABA A R-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABA A R subunits.ResultsEight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABA A R-IgG positive. Patient IgGs were always reactive with α1β3 GABA A R subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1-71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy.ConclusionsThough not as common as NMDA-R encephalitis, GABA A R encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.",
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AU - O'Connor, Kevin

AU - Waters, Patrick

AU - Komorowski, Lars

AU - Zekeridou, Anastasia

AU - Guo, Chu Yueh

AU - Mgbachi, Victor C.

AU - Probst, Christian

AU - Mindorf, Swantje

AU - Teegen, Bianca

AU - Gelfand, Jeffrey M.

AU - Geschwind, Michael D.

AU - Lennon, Vanda A

AU - Pittock, Sean J

AU - McKeon, Andrew B

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N2 - ObjectiveWe sought to validate methods for detection and confirmation of GABA A receptor (R)-IgG and clinically characterize seropositive cases.MethodsArchived serum and CSF specimens (185 total) suspected to harbor GABA A R-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABA A R-IgG positivity by IFA, based on prior reports and comparison with commercial GABA A R antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABA A R-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABA A R subunits.ResultsEight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABA A R-IgG positive. Patient IgGs were always reactive with α1β3 GABA A R subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1-71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy.ConclusionsThough not as common as NMDA-R encephalitis, GABA A R encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.

AB - ObjectiveWe sought to validate methods for detection and confirmation of GABA A receptor (R)-IgG and clinically characterize seropositive cases.MethodsArchived serum and CSF specimens (185 total) suspected to harbor GABA A R-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABA A R-IgG positivity by IFA, based on prior reports and comparison with commercial GABA A R antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABA A R-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABA A R subunits.ResultsEight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABA A R-IgG positive. Patient IgGs were always reactive with α1β3 GABA A R subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1-71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy.ConclusionsThough not as common as NMDA-R encephalitis, GABA A R encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.

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