Autoimmune epilepsy: some epilepsy patients harbor autoantibodies to glutamate receptors and dsDNA on both sides of the blood-brain barrier, which may kill neurons and decrease in brain fluids after hemispherotomy.
OBJECTIVE
Elucidating the potential contribution of specific autoantibodies (Ab's) to the etiology and/or pathology of some human epilepsies.


METHODS
Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies were tested for Ab's to the "B" peptide (amino acids 372-395) of the glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), and additional autoimmune disease-associated autoantigens, and for the ability of their serum and cerebrospinal-fluid (CSF) to kill neurons.


RESULTS
Elevated anti-GluR3B Ab' s were found in serum and CSF of most RE patients, and in serum of 17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's decreased drastically in CSF following functional-hemispherotomy, in association with seizure cessation and neurological improvement. Serum and CSF of two RE patients, and serum of 12/71 (17%) patients with other epilepsies, contained elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of "classical" autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, beta2-glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE patients caused substantial death of hippocampal neurons.


CONCLUSIONS
Some epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may be detrimental to the nervous system and/or peripheral organs, we recommend testing for their presence in epilepsy, and silencing their activity in Ab-positive patients.
Ganor
Yonatan
Y
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Goldberg-Stern
Hadassa
H
Amrom
Dina
D
Lerman-Sagie
Tally
T
Teichberg
Vivian I
VI
Pelled
Dori
D
Futerman
Anthony H
AH
Zeev
Bruria Ben
BB
Freilinger
Michael
M
Verheulpen
Denis
D
Van Bogaert
Patrick
P
Levite
Mia
M
D000293:Adolescent; D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000134:cerebrospinal fluid; D000974:Antibodies, Antinuclear / Q000097:blood / Q000134:cerebrospinal fluid; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D001812:Blood-Brain Barrier / Q000276:immunology; D016923:Cell Death; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D004827:Epilepsy / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D038421:Hemispherectomy; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology; D018091:Receptors, AMPA / Q000235:genetics / Q000276:immunology*; D053482:beta 2-Glycoprotein I; D055517:snRNP Core Proteins
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; D018091:Receptors, AMPA; C035356:SS-A antibodies; D053482:beta 2-Glycoprotein I; C104723:glutamate receptor ionotropic, AMPA 3; D055517:snRNP Core Proteins; D005968:Glutamate Decarboxylase