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  Neurofascin as a target for autoantibodies in peripheral neuropathies

Ng, J. K. M., Malotka, J., Kawakami, N., Derfuss, T., Khademi, M., Olsson, T., et al. (2012). Neurofascin as a target for autoantibodies in peripheral neuropathies. Neurology, 79(23), 2241-2248. doi:10.1212/WNL.0b013e31827689ad.

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 Creators:
Ng, Judy King Man1, Author           
Malotka, Joachim1, Author           
Kawakami, Naoto1, Author           
Derfuss, Tobias, Author           
Khademi, Mohsen, Author
Olsson, Tomas, Author
Linington, Christopher, Author           
Odaka, Masaaki, Author
Tackenberg, Bjoern, Author
Pruess, Harald, Author
Schwab, Jan M., Author
Harms, Lutz, Author
Harms, Hendrik, Author
Sommer, Claudia, Author
Rasband, Matthew N., Author
Eshed-Eisenbach, Yael, Author
Peles, Elior, Author
Hohlfeld, Reinhard1, Author           
Yuki, Nobuhiro, Author
Dornmair, Klaus1, Author           
Meinl, Edgar1, Author            more..
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

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Free keywords: GUILLAIN-BARRE-SYNDROME; EXPERIMENTAL ALLERGIC NEURITIS; RANVIER; DISRUPTION; ANTIBODIES; GLIOMEDIN; JUNCTION; PROTEIN; CELLS; NODES
 Abstract: 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-Barre 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. Neurology (R) 2012;79:22412248

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Language(s): eng - English
 Dates: 2012-12
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Neurology
Source Genre: Journal
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Publ. Info: Cleveland, Ohio [etc.] : Advanstar Communications [etc.]
Pages: - Volume / Issue: 79 (23) Sequence Number: - Start / End Page: 2241 - 2248 Identifier: ISSN: 0028-3878
CoNE: https://pure.mpg.de/cone/journals/resource/954925246073