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

摘要

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.