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Neurofascin as a target for autoantibodies in peripheral neuropathies

Ng, J. K. and Malotka, J. and Kawakami, N. and Derfuss, T. and Khademi, M. and Olsson, T. and Linington, C. and Odaka, M. and Tackenberg, B. and Pruss, H. and Schwab, J. M. and Harms, L. and Harms, H. and Sommer, C. and Rasband, M. N. and Eshed-Eisenbach, Y. and Peles, E. and Hohlfeld, R. and Yuki, N. and Dornmair, K. and Meinl, E.. (2012) Neurofascin as a target for autoantibodies in peripheral neuropathies. Neurology, Vol. 79, H. 23. pp. 2241-2248.

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Official URL: http://edoc.unibas.ch/dok/A6338641

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
UniBasel Contributors:Derfuss, Tobias Johannes
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Lancet Publications
ISSN:0028-3878
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:08 May 2015 08:45

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