title: The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.
abstract: OBJECTIVE
  The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy.
  
  
  METHODS
  Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency.
  
  
  RESULTS
  Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency.
  
  
  CONCLUSIONS
  A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.
authors.affiliation: Don Carlo Gnocchi Onlus Foundation, Milan, Italy; Department of Geriatrics, Neuroscience and Orthopedics, Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Iorio
authors.forename: G
authors.initials: G
authors.lastname: Assenza
authors.forename: M
authors.initials: M
authors.lastname: Tombini
authors.forename: G
authors.initials: G
authors.lastname: Colicchio
authors.forename: G
authors.initials: G
authors.lastname: Della Marca
authors.forename: A
authors.initials: A
authors.lastname: Benvenga
authors.forename: V
authors.initials: V
authors.lastname: Damato
authors.forename: P M
authors.initials: PM
authors.lastname: Rossini
authors.forename: C
authors.initials: C
authors.lastname: Vollono
authors.forename: D
authors.initials: D
authors.lastname: Plantone
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: A P
authors.initials: AP
authors.lastname: Batocchi
authors.forename: A
authors.initials: A
authors.lastname: Evoli
mesh_terms: D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid; D004351:Drug Resistance; D004827:Epilepsy / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001323:Autoantibodies
keywords: antiepileptic drug resistant epilepsy; autoimmune epilepsy; leucine-rich glioma inactivated 1; synaptic antigens