title: Evidence of a pathogenic role for CD8(+) T cells in anti-GABAB receptor limbic encephalitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Golombeck
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bönte
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Mönig
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Karen M
authors.initials: KM
authors.lastname: van Loo
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Hartwig
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Schwindt
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Widman
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lindenau
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Lohmann
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.affiliation: Departments of Neurology (K.S.G., K.B., C.M., M.H., H.W., S.G.M., H.L., C.C.G., N.M.) and Clinical Radiology (W.S.), and Institute of Physiology I-Neuropathophysiology (S.G.M.), University of Münster; Departments of Epileptology (G.W., C.E.E.) and Neuropathology (K.M.v.L., A.J.B.), University of Bonn; Epilepsy Center Hamburg (M.L.), Evangelisches Krankenhaus Alsterdorf, Hamburg; and Department of Neuropathology (M.G.), University of Hamburg, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Melzer