Document Detail

Neurofascin as a target for autoantibodies in peripheral neuropathies.
MedLine Citation:
PMID:  23100406     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: 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.
Judy King Man Ng; Joachim Malotka; Naoto Kawakami; Tobias Derfuss; Mohsen Khademi; Tomas Olsson; Christopher Linington; Masaaki Odaka; Björn Tackenberg; Harald Prüss; Jan M Schwab; Lutz Harms; Hendrik Harms; Claudia Sommer; Matthew N Rasband; Yael Eshed-Eisenbach; Elior Peles; Reinhard Hohlfeld; Nobuhiro Yuki; Klaus Dornmair; Edgar Meinl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-24
Journal Detail:
Title:  Neurology     Volume:  79     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-05     Completed Date:  2013-02-04     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2241-8     Citation Subset:  AIM; IM    
Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
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MeSH Terms
Autoantibodies / blood*
Cell Adhesion Molecules / immunology*
Nerve Growth Factors / immunology*
Neuritis, Autoimmune, Experimental / blood,  immunology*
Peripheral Nervous System Diseases / blood,  immunology*
Rats, Inbred Lew
Grant Support
Reg. No./Substance:
0/Autoantibodies; 0/Cell Adhesion Molecules; 0/NFASC protein, human; 0/Nerve Growth Factors
Comment In:
Neurology. 2012 Dec 4;79(23):2224-5   [PMID:  23100403 ]

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