GABA A receptor autoimmunity: A multicenter experience.

Objective: We sought to validate methods for detection and confirmation of GABA _A receptor (R)-IgG and clinically characterize seropositive cases.
Methods: Archived 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.
Results: Eight 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.
Conclusions: Though 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.