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Journal of Neuroscience, Vol 14, 6230-6238, Copyright © 1994 by Society for Neuroscience
Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis
DJ Miller, KS Sanborn, JA Katzmann and M Rodriguez
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Susceptible strains of mice infected intracerebrally with Theiler's murine
encephalomyelitis virus develop a chronic, progressive, immune- mediated
CNS demyelinating disease similar both pathologically and clinically to
multiple sclerosis. Previous reports indicated that polyclonal
immunoglobulins from mice injected with homogenized spinal cord promote CNS
remyelination when given to SJL/J mice chronically infected with Theiler's
virus. To explore further both the mechanism(s) and potential therapeutic
usefulness of antibodies in the treatment of CNS demyelinating diseases, we
made a panel of monoclonal antibodies derived from splenocytes of SJL/J
mice injected with homogenized spinal cord, and screened them for their
autoantigen-binding capability. Monoclonal IgM autoantibodies from two
clones, designated SCH94.03 and SCH94.32, promoted fourfold more CNS
remyelination than controls when given to chronically infected SJL/J mice.
CNS remyelination, assessed morphologically by the presence of abnormally
thin myelin sheaths relative to axonal diameter, correlated with the
absence of clinical disease progression. In titration experiments,
treatment with SCH94.03 and remyelination had a positive dose-response
relationship, and as little as 10 micrograms of antibody promoted
remyelination. Both SCH94.03 and SCH94.32 showed multiorgan autoreactivity,
and recognized both surface and cytoplasmic determinants on glial cells. We
propose that this model provides a unique system to elucidate the
mechanism(s) and test the reparative potential of autoantibodies in the
treatment of CNS injury.
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