Evidence of a pathogenic role for CD8(+) T cells in anti-GABAB receptor limbic encephalitis

OBJECTIVES: To characterize the cellular autoimmune response in patients with γ-aminobutyric acid (GABA)B receptor antibody-associated limbic encephalitis (GABAB-R LE).

METHODS: Patients underwent MRI, extensive neuropsychological assessment, and multiparameter flow cytometry of peripheral blood and CSF.

RESULTS: We identified a series of 3 cases of nonparaneoplastic GABAB-R LE and one case of paraneoplastic GABAB-R LE associated with small cell lung cancer. All patients exhibited temporal lobe epilepsy, neuropsychological deficits, and MRI findings typical of LE. Absolute numbers of CD19(+) B cells, CD138(+) CD19(+) plasma cells, CD4(+) T cells, activated HLADR(+) CD4(+) T cells, as well as CD8(+) T cells and HLADR(+) CD8(+) T cells did not differ in peripheral blood but were elevated in CSF of patients with GABAB-R LE compared to controls. Augmented absolute numbers of CD138(+) CD19(+) plasma cells and activated HLADR(+) CD8(+) T cells in CSF corresponded to higher overall neuropsychological and memory deficits in patients with GABAB-R LE. A histologic specimen of one patient following selective amygdalohippocampectomy revealed perivascular infiltrates of CD138(+) plasma cells and CD4(+) T cells, whereas cytotoxic CD8(+) T cells were detected within the brain parenchyma in close contact to neurons.

CONCLUSION: Our data suggest a pathogenic role for CD8(+) T cells in addition to the established role of plasma cell-derived autoantibodies in GABAB-R LE.