Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-4-6
pubmed:abstractText
Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as NF-L has so far been ignored. Here we show that Biozzi ABH mice immunized with NF-L protein develop neurologic disease characterized by spastic paresis and paralysis concomitant with axonal degeneration and inflammation primarily in the dorsal column of the spinal cord. The inflammatory central nervous system lesions were dominated by F4/80+ macrophages/microglia and relatively low numbers of CD4+ and CD8+ T-cells. In splenocyte cultures, proliferation to NF-L was observed in CD4+ T-cells accompanied by the production of the proinflammatory cytokine interferon-gamma. Elevated levels of circulating antibodies recognizing recombinant mouse NF-L were present in the serum, and immunoglobulin deposits were observed within axons in spinal cord lesions of mice exhibiting clinical disease. These data provide evidence that autoimmunity to NF-L protein induces axonal degeneration and clinical neurologic disease in mice, indicating that autoimmunity to axonal antigens, as described in multiple sclerosis, may be pathogenic rather than acting merely as a surrogate marker for axonal degeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
295-304
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17413320-Animals, pubmed-meshheading:17413320-Antibodies, pubmed-meshheading:17413320-Axons, pubmed-meshheading:17413320-CD4-Positive T-Lymphocytes, pubmed-meshheading:17413320-CD8-Positive T-Lymphocytes, pubmed-meshheading:17413320-Cell Proliferation, pubmed-meshheading:17413320-Cytokines, pubmed-meshheading:17413320-Female, pubmed-meshheading:17413320-Flow Cytometry, pubmed-meshheading:17413320-Immunization, pubmed-meshheading:17413320-Male, pubmed-meshheading:17413320-Mice, pubmed-meshheading:17413320-Mice, Biozzi, pubmed-meshheading:17413320-Microscopy, Electron, Transmission, pubmed-meshheading:17413320-Muscle Spasticity, pubmed-meshheading:17413320-Myelin Proteins, pubmed-meshheading:17413320-Myelin-Associated Glycoprotein, pubmed-meshheading:17413320-Nervous System Diseases, pubmed-meshheading:17413320-Neurofilament Proteins, pubmed-meshheading:17413320-Sciatic Nerve, pubmed-meshheading:17413320-Spinal Cord
pubmed:year
2007
pubmed:articleTitle
Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice.
pubmed:affiliation
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't