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

PURPOSE:

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: Yonatan Ganor, Hadassa Goldberg-Stern, Dina Amrom, Tally Lerman-Sagie, Vivian I Teichberg, Dori Pelled, Anthony H Futerman, Bruria Ben Zeev, Michael Freilinger, Denis Verheulpen, Patrick Van Bogaert, Mia Levite
• Journal: Clinical & developmental immunology (Clin Dev Immunol) 2004 Sep-Dec Vol. 11 Issue 3-4 Pg. 241-52 ISSN: 1740-2522 [Print] Egypt
• PMID: 15559370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anticardiolipin
• Antibodies, Antinuclear
• Autoantibodies
• Autoantigens
• Glycoproteins
• Receptors, AMPA
• SS-A antibodies
• beta 2-Glycoprotein I
• glutamate receptor ionotropic, AMPA 3
• snRNP Core Proteins
• Glutamate Decarboxylase

Topics

• Adolescent
• Amino Acid Sequence
• Antibodies, Anticardiolipin (blood, cerebrospinal fluid)
• Antibodies, Antinuclear (blood, cerebrospinal fluid)
• Autoantibodies (blood, cerebrospinal fluid)
• Autoantigens
• Autoimmune Diseases (immunology, pathology, surgery)
• Blood-Brain Barrier (immunology)
• Cell Death
• Cells, Cultured
• Child
• Child, Preschool
• Encephalitis (immunology, pathology, surgery)
• Epilepsy (immunology, pathology, surgery)
• Female
• Glutamate Decarboxylase (immunology)
• Glycoproteins (immunology)
• Hemispherectomy
• Hippocampus (pathology)
• Humans
• Male
• Molecular Sequence Data
• Neurons (pathology)
• Receptors, AMPA (genetics, immunology)
• beta 2-Glycoprotein I
• snRNP Core Proteins