Antibodies to AMPA receptors in Rasmussen's encephalitis. (March 2016)

• Record Type: Journal Article
• Authors: Nibber, Anjan; Clover, Linda; Pettingill, Philippa; Waters, Patrick; Elger, Christian E.; Bien, Christian G.; Vincent, Angela; Lang, Bethan
• Is Part Of: European journal of paediatric neurology. Volume 20:Number 2(2016:Mar.)
• Page Start: 222
• Page End: 227
• Publication Date: 2016-03
• Subjects: Autoantibodies -- Rasmussen's encephalitis -- AMPA receptors; Abs antibodies -- AED anti-epileptic drugs -- AMPAR amino-3-hydroxy-5-methyl-4-isoxazolepproprionic acid receptor -- BBB blood brain barrier -- CASPR2 contactin-associated protein receptor like 2 -- CBA cell based assay -- CNS central nervous system -- CSF cerebrospinal fluid -- DC disease control -- EPC epilepsia partialis continua -- GABAAR gamma-aminobutryric acid receptor A -- GABABR gamma-aminobutryric acid receptor B -- HC healthy control -- HEK human embryonic kidney cells -- HR hemispheric ratio -- LGI1 leucine glioma inactivated protein -- MRI magnetic resonance image -- NMDAR N-methyl-d-asparate receptor -- RE Rasmussen's encephalitis -- VGKC voltage gated potassium channel; Pediatric neurology -- Periodicals; Nervous System Diseases -- Periodicals; Child -- Periodicals; Infant -- Periodicals; Neurologie pédiatrique -- Périodiques; Pediatric neurology; Electronic journals; Periodicals; Electronic journals; 618.928
• DOI: 10.1016/j.ejpn.2015.12.011
• Languages: English
• ISSNs: 1090-3798

Abstract

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 (GABAA R α1/γ2/β2 and GABAB R 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. Highlights: Fifty two patients with Rasmussen's Encephalitis were tested for antibodies to AMPA receptors using cell-based assays. Two patients (3.8%) had antibodies to AMPA receptors comprising of GluA2/3 co-expressed together. No sera showed reactivity to the singly transfected receptors (GluA1, 2 or 3) or to co-expressed GluA1/2. Ten patients (including both patients with antibodies that bound GluA2/3) bound to the surface of cultured neurones. The antibodies detected to GluA2/3 may represent a biomarker of the inflammatory nature of the disease.