Human antibodies accelerate the rate of remyelination following lysolecithin-induced demyelination in mice

Allan J. Bieber, Arthur Warrington, Kuni Asakura, Bogoljub Ciric, Srini V. Kaveri, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Immunoglobulin-based therapies are becoming increasingly common for the treatment of neurologic and autoimmune diseases in humans. In this study, we demonstrate that systemic administration of either polyclonal human immunoglobulins or specific human monoclonal antibodies can accelerate the rate of CNS remyelination following toxin-induced demyelination. Injection of lysolecithin directly into the spinal cord results in focal demyelinated lesions. In contrast to other murine models of demyelinating disease, the mechanism of demyelination following lysolecithin injection is independent of immune system activation, and chronic inflammation at the site of the lesion is minimal. Administration of polyclonal human IgM (pHIgM) or a serum-derived human monoclonal antibody (sHIgM22) resulted in approximately a twofold increase in remyelinating axons when compared to animals treated with saline or with antibodies that do not promote repair. Both pHIgM and sHIgM22 show strong binding to CNS white matter and oligodendrocytes, while antibodies that did not accelerate remyelination do not. This differential staining pattern suggests that enhanced remyelination may result from direct stimulation of oligodendrocyte remyelination by binding to surface receptors on oligodendrocytes or glial progenitor cells. We propose the use of human polyclonal IgM or specific human monoclonal IgM antibodies as potential therapies to enhance myelin repair following CNS injury and disease.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalGlia
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2002

Keywords

  • Immunoglobulin
  • Lysolecithin
  • Multiple sclerosis
  • Remyelination

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Bieber, A. J., Warrington, A., Asakura, K., Ciric, B., Kaveri, S. V., Pease, L. R., & Rodriguez, M. (2002). Human antibodies accelerate the rate of remyelination following lysolecithin-induced demyelination in mice. Glia, 37(3), 241-249. https://doi.org/10.1002/glia.10033