title: Neurofascin as a target for autoantibodies in peripheral neuropathies.
abstract: OBJECTIVE
  We asked whether autoantibodies against neurofascin (NF)186 or NF155, both localized at the nodes of Ranvier, are present in serum of patients with inflammatory neuropathy, and whether NF-specific monoclonal antibodies are pathogenic in vivo.
  
  
  METHODS
  We cloned human NF155 and NF186, and developed an ELISA and cell-based assay to screen for antibodies to human NF in a total of 434 donors including 294 patients with Guillain-Barré syndrome variants acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy, and chronic inflammatory demyelinating polyneuropathy (CIDP). We characterized reactive samples by isotyping, tissue section staining, and epitope mapping. We also injected NF-specific monoclonal antibodies IV into rats with experimental autoimmune neuritis.
  
  
  RESULTS
  We detected autoantibodies to NF by ELISA in 4% of patients with AIDP and CIDP, but not in controls. Most positive samples contained immunoglobulin G (IgG)1, IgG3, or IgG4 antibodies directed to only one isoform of NF. Two patients with CIDP showed particularly high (1:10,000 dilution) NF155-specific reactivity in both assays and stained paranodes. Two other patients with CIDP who benefited from plasma exchange exhibited antibodies to NF155 by ELISA, and upon affinity purification, antibodies to both isoforms were observed by both assays. Anti-NF monoclonal antibodies enhanced and prolonged induced neuritis in rats.
  
  
  CONCLUSIONS
  Autoantibodies to NF are detected in a very small proportion of patients with AIDP and patients with CIDP, but may nevertheless be pathogenic in these cases.
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Judy King Man
authors.initials: JK
authors.lastname: Ng
authors.forename: Joachim
authors.initials: J
authors.lastname: Malotka
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
authors.forename: Masaaki
authors.initials: M
authors.lastname: Odaka
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schwab
authors.forename: Lutz
authors.initials: L
authors.lastname: Harms
authors.forename: Hendrik
authors.initials: H
authors.lastname: Harms
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed-Eisenbach
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D006801:Humans; D009414:Nerve Growth Factors / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology*; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; C054305:NFASC protein, human; D009414:Nerve Growth Factors