title: Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors with neuropsychiatric systemic lupus erythematosus.
abstract: OBJECTIVE
  To determine epitope reactivity of autoantibodies to N-methyl-D-aspartate (NMDA) receptor NR1 subunit and their association with neuropsychiatric systemic lupus erythematosus (NPSLE).
  
  
  METHODS
  Paired serum and CSF specimens were obtained from 41 patients with NPSLE (22 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 19 with neurologic syndromes or polyneuropathy [focal NPSLE]), 21 patients with various rheumatic diseases other than SLE (non-SLERD). Sera were also obtained from 27 SLE patients without neuropsychiatric manifestations (non-CNS SLE). Antibodies to murine NR1 (mNR1) or to 4 different preparations of synthetic 25-amino-acid (AA) peptides of human NR1 were measured by enzyme-linked immune sorbent assay (ELISA).
  
  
  RESULTS
  Serum anti-mNR1 levels were significantly higher in NPSLE than in non-SLERD. Sera from NPSLE patients bound efficiently to the AA residues 19-44 from the N-terminus of NR1 (NR1-A) or 56-81 (NR1-C). Accordingly, serum anti-NR1-A and anti-NR1-C were also elevated in NPSLE compared with non-SLERD. Of note, anti-NR1-A as well as anti-NR1-C levels in CSF, but not in sera, were significantly elevated in diffuse NPSLE compared with focal NPSLE or with non-SLERD.
  
  
  CONCLUSIONS
  These results suggest that autoantibodies to NMDA receptor NR1, especially to the AA residues 19-44 and 56-81 from the N-terminus play a pivotal role in the pathogenesis of diffuse NPSLE.
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nagai
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Arinuma
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000276:immunology*; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Autoantibodies; Cerebrospinal fluid; Neuropsychiatric systemic lupus erythematosus