Anti–GABAB Receptor (GABABR) Antibodies

This laboratory assay detects IgG autoantibodies against the gamma-aminobutyric acid type B receptor (GABABR), a G-protein–coupled metabotropic receptor for the neurotransmitter GABA. GABABR is widely distributed in the spinal cord, cerebellum, diencephalon (thalamus, hypothalamus) and telencephalon (striatum, globus pallidus, hippocampus). It regulates inhibitory synaptic activity with both presynaptic actions – reducing release of excitatory neurotransmitters (e.g., glutamate) by modulating voltage-gated calcium channels and exocytosis – and postsynaptic actions—inducing slow inhibitory currents that modulate neuronal excitability.

Autoimmune encephalitis mediated by anti-GABABR antibodies predominantly involves the limbic system, affects mainly middle-aged and older men, and typically has a rapid onset. Antibodies interfere with receptor function, promoting neuronal hyperexcitability and causing clinical manifestations such as epilepsy (often the first symptom), cognitive dysfunction, behavioural/psychiatric changes and occasionally cerebellar ataxia. About half of patients have an underlying tumour, most commonly small-cell lung carcinoma (SCLC), often presenting as paraneoplastic limbic encephalitis. Anti-GABABR testing is essential for the differential diagnosis of autoimmune encephalitides and for therapeutic management, enabling prompt initiation of immunosuppressive therapy; it is also useful for disease monitoring and screening for associated neoplasms. Results should always be interpreted in the context of clinical findings and other laboratory and instrumental data.