GABA _B receptor autoantibody frequency in service serologic evaluation

Abstract

Objective: Small-cell lung carcinoma (SCLC) and limbic encephalitis are recognized g-aminobutyric acid-B receptor (GABA B R) autoantibody accompaniments. We sought to determine in a diagnostic serology laboratory the frequency and accompaniments (neurologic, oncologic, and serologic) of GABA B R-immunoglobulin G (IgG). Methods:We tested stored serum and CSF specimens from 3 patient groups for GABA B R-IgG by indirect immunofluorescence on mouse brain tissue and transfected HEK293 cells. Group 1 included 3,989 patients tested for GABA B R-IgG in service evaluation for suspected autoimmune encephalopathy. Group 2 included 49 patients with an unclassified CNS synaptic IgG detected (antedating descriptions of GABA B R autoantibody). Group 3 included 384 patients in whom $1 SCLC-predictive autoantibodies had been detected.Results: GABA B R-specific IgG was detected in 17 patients (serum, 14; CSF, 11). N-type calcium channel antibody coexisted with GABA B R-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 GABA B R-IgG.Conclusion: GABA B R autoantibody is a marker of an uncommon but treatable paraneoplastic neurologic disorder, usually occurring in the setting of limbic encephalitis and SCLC. Autoantibodies specific for the CNS inhibitory g-aminobutyric acid-B receptor (GABA B R, B1 and B2 subunits) have been reported in patients with paraneoplastic limbic encephalitis (LE). Small-cell lung carcinoma (SCLC) and other neuroendocrine neoplasms 1,2 have been reported as oncologic accompaniments. The neuronal N-type voltage-gated calcium channel antibody, another paraneoplastic autoantibody SCLC marker, is commonly reported as a serologic accompaniment.1 Paraneoplastic neurologic disorders associated with autoantibodies targeting neural plasma membrane antigens (e.g., GABA B R) tend to improve with early cancer treatment and immunotherapy.1 In contrast, disorders associated with autoantibodies specific for neural intracellular antigens (i.e., nuclear and cytoplasmic) are less responsive to these treatments.To date, most patients reported with GABA B R antibody have been ascertained through evaluation of patients with LE.1,2 Autoimmune serologic evaluation in a clinical service laboratory, involving patients with diverse neurologic presentations, allows broader ascertainment of clinical associations. Here, we report the detection frequency of GABA B R antibody and associ...

Paraneoplastic neurologic disorders in small cell lung carcinoma

“…In keeping with a previous study, 20 we found that GABAb receptor antibodies coexist with both N-and P/Q-type VGCC antibodies in LE (the previous study recruited large numbers of patients with LE and demonstrated that GABAb receptor antibodies cosegregate with N-type VGCC more than P/Q-type in LE). In addition, we found that 20% of SCLC LEMS patients (a P/Q VGCC antibody-mediated disease) were GABAb receptor antibody-positive.…”

Limbic encephalitis due to GABABand AMPA receptor antibodies: a case series

“…Previous publications expanded the clinical picture of GABA B R abs to cerebellar ataxia, opsoclonus-myoclonus syndrome and progressive encephalomyelopathy 3 4 8. We found some of these symptoms in parallel with LE but not in isolation.…”

“…This was done to confirm, extend and refine the data from the original series presented by the Philadelphia/Barcelona groups2 5 and confirmed by the Mayo group 8. LE was defined by at least two of the following: seizures of temporal semiology, disturbance of episodic memory, affective disturbances with prominent mood lability, or disinhibition 9.…”

Anti-GABAB Receptor Encephalitis in China

“…It has been reported that patients with SCLC might have unfavorable treatment outcomes if using the immunotherapy. And the main causes of death in patients with anti-GABA B R encephalitis were lung tumor progression and chemotherapy related complications [2,6,10]. Therefore, it is necessary to attach great importance to the detection of tumor or paraneoplastic biomarkers.…”