Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice

Ruth Huizinga, Nicole Heijmans, Pia Schubert, Steve Gschmeissner, Bert A 't Hart, Harald Herrmann, Sandra Amor

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)295-304
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number4
Publication statusPublished - Apr 2007


  • Animals
  • Antibodies
  • Axons
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Proliferation
  • Cytokines
  • Female
  • Flow Cytometry
  • Immunization
  • Journal Article
  • Male
  • Mice
  • Mice, Biozzi
  • Microscopy, Electron, Transmission
  • Muscle Spasticity
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Nervous System Diseases
  • Neurofilament Proteins
  • Research Support, Non-U.S. Gov't
  • Sciatic Nerve
  • Spinal Cord

Cite this