title: Antibodies to AMPA receptors in Rasmussen's encephalitis.
abstract: Rasmussen's encephalitis is a rare progressive childhood disorder characterized by frequent severe seizures, hemiparesis, encephalitis and mental deterioration, and associated with severe unilateral neuroinflammation. Autoantibodies, particularly to the GluA3 subtype of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propinonic acid receptor (AMPAR) were reported in the 1990s but not always confirmed. To explore further, sera from 52 patients with Rasmussen's encephalitis were tested by cell-based assays for antibodies to AMPAR GluA1/2/3, N-methyl-d-aspartate (NMDA NR1/2b), γ-aminobutyric acid type A and B (GABAAR α1/γ2/β2 and GABABR b1/b2) receptors, for potassium channel complex proteins, and for binding to live cortical and hippocampal neuronal cultures. Two patients' sera (3.8%) bound to HEK cells co-transfected with the GluA2 and GluA3 subunits. One additional patient had a low level of VGKC-complex antibodies. These three, and seven additional, sera bound to hippocampal cultures. No other antibodies were detected. Thus, despite the rarity of GluA2/3 antibodies, 10 patients (19.2%) had evidence of antibodies to neuronal antigens. Whether these antibodies play a primary role in RE, or appear secondary to the neuro-inflammatory damage in this highly destructive disease, requires further study.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Anjan
authors.initials: A
authors.lastname: Nibber
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Clover
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Philippa
authors.initials: P
authors.lastname: Pettingill
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.affiliation: Epilepsy Centre Bethel, Krankenhaus Mara, Bielefeld, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. Electronic address: bethan.lang@ndcn.ox.ac.uk.
authors.forename: Bethan
authors.initials: B
authors.lastname: Lang
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D018091:Receptors, AMPA / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018091:Receptors, AMPA
keywords: AMPA receptors; Autoantibodies; Rasmussen's encephalitis