GABAB receptor autoantibody frequency in service serologic evaluation

Abstract

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.

Figure 1. Synaptic staining pattern of γ-aminobutyric acid-B receptor–immunoglobulin G compared with NMDA-R-IgG staining pattern (tissue immunofluorescence)

The γ-aminobutyric acid-B receptor (GABA_BR)–immunoglobulin G (IgG) binding in the cerebrum (A) is most prominent in the thalamus (t), and is also seen in hippocampus (h), cerebral cortex (cx), and striatum (s). GABA_BR-IgG also binds to cerebellum (B, both molecular [m] and granular [g] layers), midbrain (mb, panel C), and myenteric neurons (arrowheads). In contrast, NMDA-R-IgG binding is most prominent in the hippocampus (h, panel D) and cerebellar granular layer (g, panel E); myenteric neurons are not stained (not shown).

Figure 2. MRI of thoracic spine of patient 8 demonstrates a longitudinally extensive T2 signal abnormality in the thoracic cord (sagittal image, A) that had central cord predominance (axial image, B)