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.