title: Antibodies to glutamate receptor subtype 3 (GluR3) are found in some patients suffering from epilepsy as the main disease, but not in patients whose epilepsy accompanies antiphospholipid syndrome or Sneddon's syndrome.
abstract: Autoantibodies (Ab's) to the "B" peptide (amino acids 372-395) of glutamate/AMPA receptor subtype 3 (GluR3) are found in serum and cerebrospinal fluid of some patients with different types of epilepsy. Since such anti-GluR3B Ab's can activate and/or kill neurons in vitro and in vivo, they may contribute to epilepsy. To investigate whether anti-GluR3B Ab's may also be relevant to epilepsy when it accompanies some autoimmune-diseases, we tested for these Ab's in patients suffering from epilepsy that accompanies anti-phospholipid syndrome (APS) or Sneddon's syndrome (SNS), both being autoimmune-diseases with frequent neurological complications. We tested 77 pediatric patients whose epilepsy is their main disease; 31 adult patients whose epilepsy accompanies APS (primary or SLE-associated) or SNS; 45 epilepsy-free APS and SNS patients; and 90 healthy controls. Compared to the controls, significantly elevated anti-GluR3B Ab's were found in 22/77 (29%) patients whose epilepsy is their main disease, but in none of the patients whose seizures accompany APS or SNS. Yet, all the APS and SNS patients harbored the characteristic anti-phospholipid Ab's (aPL), directed against cardiolipin and beta2-glycoprotein I, and had lupus anti-coagulant. Thus, anti-GluR3B Ab's are not crossreactive with aPL, and not produced as a non-specific consequence of seizures on the one hand, or autoimmune-diseases on the other. Taken together with new findings accumulated recently in our lab, we suggest that anti-GluR3B Ab's are produced primarily in the periphery due to specific/non-specific "irritation" of the immune system, and that once they reach the brain via a leaky blood-brain barrier they may cause neuronal/glial damage and facilitate the outburst of epilepsy and additional neurological abnormalities. In contrast, the presence of anti-GluR3B Ab's does not seem to increase the probability of developing APS, SNS or the seizures that often accompany these autoimmune-diseases. These findings may have important diagnostic and therapeutic implications.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Ganor
authors.forename: H
authors.initials: H
authors.lastname: Goldberg-Stern
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: L A
authors.initials: LA
authors.lastname: Dobrynina
authors.forename: L
authors.initials: L
authors.lastname: Kalashnikova
authors.forename: M
authors.initials: M
authors.lastname: Levite
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology*; D002648:Child; D004827:Epilepsy / Q000150:complications / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018091:Receptors, AMPA / Q000276:immunology*; D018860:Sneddon Syndrome / Q000150:complications / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3