Therapeutics to promote CNS repair: A natural human neuron-binding igm regulates membrane-raft dynamics and improves motility in a mouse model of multiple sclerosis

Xiaohua Xu, Aleksandar Denic, Arthur E. Warrington, Allan J. Bieber, Moses Rodriguez

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We have discovered a role for natural autoantibodies in central nervous system repair, remyelination and axon protection. These natural human antibodies are of the immunoglobulin M (IgM) isotype, and they bind to the surface of neural cells. The epitope of the antibody includes sialic acid because treatment with sialidase disrupts the binding. A fully human recombinant form of one of these IgMs, rHIgM12, has the same properties as the serum-derived IgM. rHIgM12 enhanced polarized axonal outgrowth from primary neurons when presented as a substrate in vitro and improved motor functions in chronically Theiler's virus-infected SJL mice, a model of MS. rHIgM12 bound to neuronal surfaces and induced cholesterol and ganglioside (GM1) clustering, indicating that rHIgM12 functions through a mechanism of axonal membrane stabilization. Our work demonstrates that a natural human neuron-binding IgM can regulate membrane domain dynamics. This antibody has the potential to improve neurologic disease.

Original languageEnglish (US)
Pages (from-to)S50-S56
JournalJournal of Clinical Immunology
Volume33
Issue numberSUPPL.1
DOIs
StatePublished - Jan 1 2013

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Keywords

  • CNS repair
  • IgM
  • membrane raft
  • motility
  • multiple sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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