Serum antibodies in epilepsy and seizure-associated disorders.
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.
McKnight
K
K
Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom.
Jiang
Y
Y
Hart
Y
Y
Cavey
A
A
Wroe
S
S
Blank
M
M
Shoenfeld
Y
Y
Vincent
A
A
Palace
J
J
Lang
B
B
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000503:physiopathology; D004827:Epilepsy / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000172:deficiency / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D009419:Nerve Tissue Proteins / Q000276:immunology; D009433:Neural Inhibition / Q000276:immunology; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011237:Predictive Value of Tests; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000172:deficiency
D000941:Antigens; D001323:Autoantibodies; D007155:Immunologic Factors; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase