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SHR Neuro Cancer Cardio Lipid Metab Microb

Mathey, EK; Derfuss, T; Storch, MK; Williams, KR; Hales, K; Woolley, DR; Al-Hayani, A; Davies, SN; Rasband, MN; Olsson, T; Moldenhauer, A; Velhin, S; Hohlfeld, R; Meinl, E; Linington, C.
Neurofascin as a novel target for autoantibody-mediated axonal injury.
J Exp Med. 2007; 204(10):2363-2372 Doi: 10.1084/jem.20071053 [OPEN ACCESS]
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Co-authors Med Uni Graz

Storch Maria

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Abstract:

Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics-based approach, we identified neurofascin-specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both neurofascin 186 (NF186), a neuronal protein concentrated in myelinated fibers at nodes of Ranvier, and NF155, the oligodendrocyte-specific isoform of neurofascin. Our in vitro studies with hippocampal slice cultures indicate that neurofascin antibodies inhibit axonal conduction in a complement-dependent manner. To evaluate whether circulating antineurofascin antibodies mediate a pathogenic effect in vivo, we cotransferred these antibodies with myelin oligodendrocyte glycoprotein-specific encephalitogenic T cells to mimic the inflammatory pathology of MS and breach the blood-brain barrier. In this animal model, antibodies to neurofascin selectively targeted nodes of Ranvier, resulting in deposition of complement, axonal injury, and disease exacerbation. Collectively, these results identify a novel mechanism of immune-mediated axonal injury that can contribute to axonal pathology in MS.

Find related publications in this database (using NLM MeSH Indexing)

Animals -

Autoantibodies - immunology

Autoantigens - immunology

Axons - immunology

Cell Adhesion Molecules - immunology

Central Nervous System - immunology

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Electrophysiology - immunology

Encephalomyelitis, Autoimmune, Experimental - immunology

Hela Cells - immunology

Humans - immunology

Multiple Sclerosis - immunology

Myelin Sheath - metabolism

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