Objective: Small-cell lung carcinoma (SCLC) and limbic encephalitis are recognized γ-aminobutyric acid-B receptor (GABABR) autoantibody accompaniments. We sought to determine in a diagnostic serology laboratory the frequency and accompaniments (neurologic, oncologic, and serologic) of GABABR-immunoglobulin G (IgG).
Methods: We tested stored serum and CSF specimens from 3 patient groups for GABABR-IgG by indirect immunofluorescence on mouse brain tissue and transfected HEK293 cells. Group 1 included 3,989 patients tested for GABABR-IgG in service evaluation for suspected autoimmune encephalopathy. Group 2 included 49 patients with an unclassified CNS synaptic IgG detected (antedating descriptions of GABABR autoantibody). Group 3 included 384 patients in whom ≥1 SCLC-predictive autoantibodies had been detected.
Results: GABABR-specific IgG was detected in 17 patients (serum, 14; CSF, 11). N-type calcium channel antibody coexisted with GABABR-IgG in all seropositive patients of groups 1 and 2. In group 1, 7 of 3,989 patients were positive (0.2%). All had limbic encephalitis; 5 had SCLC. Four patients received immunotherapy and improved neurologically. In group 2, 5 of 49 patients were positive (10%). Three had limbic encephalitis, 1 had rapidly progressive encephalomyelopathy, and 1 had cerebellar ataxia. Two patients had SCLC and 1 had multiple myeloma. In group 3, 5 of 384 patients were positive (1.3%); titers were low (detected only by transfected cell assay). The neurologic presentations were diverse and attributable to coexisting T-cell-mediated autoimmunity (indicated by CRMP-5 IgG [2], ANNA-1 [2], and ANNA-3 [2]), rather than to GABABR-IgG.
Conclusion: GABABR autoantibody is a marker of an uncommon but treatable paraneoplastic neurologic disorder, usually occurring in the setting of limbic encephalitis and SCLC.