title: 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.
abstract: 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.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Ganor
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.forename: Dina
authors.initials: D
authors.lastname: Amrom
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
authors.forename: Dori
authors.initials: D
authors.lastname: Pelled
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
authors.forename: Bruria Ben
authors.initials: BB
authors.lastname: Zeev
authors.forename: Michael
authors.initials: M
authors.lastname: Freilinger
authors.forename: Denis
authors.initials: D
authors.lastname: Verheulpen
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Bogaert
authors.forename: Mia
authors.initials: M
authors.lastname: Levite
mesh_terms: 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
chemical_list: 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