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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Neurofascin as a novel target for autoantibody-mediated axonal injury
Journal of Experimental Medicine, Volume 204, No. 10, Year 2007
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Description
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. JEM © The Rockefeller University Press.
Authors & Co-Authors
Mathey, Emily K.
Unknown Affiliation
Derfuss, Tobias J.
Unknown Affiliation
Storch, Maria K.
Unknown Affiliation
Williams, Kieran R.
Unknown Affiliation
Hales, Kimberly
Unknown Affiliation
Woolley, David R.
Unknown Affiliation
Al-Hayani, Abdulmonem A.
Unknown Affiliation
Davies, Steven N.
Unknown Affiliation
Rasband, Matthew N.
Unknown Affiliation
Olsson, Tomas P.
Unknown Affiliation
Moldenhauer, Anja
Unknown Affiliation
Velhin, Sviataslau
Unknown Affiliation
Hohlfeld, Reinhard
Unknown Affiliation
Meinl, Edgar
Unknown Affiliation
Linington, Christopher
Unknown Affiliation
Statistics
Citations: 393
Authors: 15
Affiliations: 11
Identifiers
Doi:
10.1084/jem.20071053
ISSN:
00221007
e-ISSN:
00221007
Research Areas
Disability
Violence And Injury