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From the Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford (Drs. McKnight, Vincent, and Lang and Y. Jiang); Department of Clinical Neurology, Radcliffe Infirmary, Oxford (Drs. Hart and Palace and A. Cavey); National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom (Dr. Wroe); and Department of Internal Medicine B and The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel (Drs. Blank and Shoenfeld).
Address correspondence and reprint requests to Dr. Bethan Lang, Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom; e-mail: blang{at}hammer.imm.ox.ac.uk
Objective: To investigate whether autoantibodies to ion channels and other neural antigens are present in the sera of patients with epilepsy and seizure-related diseases.
Methods: Sera were obtained from 139 patients, including 26 with preexisting autoimmune disease, 46 in whom an autoimmune basis was suspected, and 67 with drug-resistant epilepsy. The sera were assayed for antibodies to voltage-gated potassium (VGKC) and calcium (VGCC) channels, glutamic acid decarboxylase (GAD), gangliosides, glutamate receptor type 3, cardiolipins, DNA, and nuclear antigens; the results were compared with results from a large cohort of healthy and disease controls.
Results: Increased titers of VGKC antibodies (>100 pM) were detected in 16 of 139 (11%) patients with seizures but only 1 control (0.5%). Eight VGKC-positive patients presented with an acute/subacute illness, and 5 of these had the highest VGKC antibodies; 3 patients improved spontaneously, another 5 patients responded well to immunomodulatory therapy. The other VGKC-positive patients had longer disease duration (>6 years) and intermediate levels of antibodies; immunotherapies have not been tested in this group. Very high levels of GAD antibodies (>1,000 U) were found in an additional 3 patients (2.1%) with long-standing drug-resistant epilepsy.
Conclusions: The presence of autoantibodies to voltage-gated potassium channels and glutamic acid decarboxylase suggests that the immune system may contribute to certain forms of epilepsy or seizure-associated disorders. Further studies are needed to determine whether the antibodies are pathogenic.
Editorial, see page 1688
See also pages 1701 and 1802
Y.J. and B.L. were funded by a grant from the Sir Henry Wellcome Commemorative Award Scheme (SHoWCASe), and K.M. was supported by the Medical Research Council of Great Britain.
Disclosure: The authors report no conflicts of interest.
Received March 24, 2005. Accepted in final form August 11, 2005.
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