Intravenous immunoglobulin (
IVIG) is widely used for treatment of autoimmune
neurological disorders and is currently in clinical trials as a
therapy for
multiple sclerosis. We have previously demonstrated that certain mouse
monoclonal antibodies of the
IgM isotype, promote significant remyelination when administered to mice with chronic Theiler's murine encephalomyelitis virus-induced
demyelinating disease. These
IgM antibodies bind to
antigens expressed on oligodendrocytes. We now demonstrate that polyclonal human
IgG (
IVIG) and polyclonal human
IgM also promote remyelination in this system. Although both polyclonal human
IgG and
IgM promote remyelination,
IgM is more potent. Polyclonal human
IgM also differs from human
IgG in its ability to bind strongly to
antigens expressed in the CNS and by oligodendrocytes. We propose that polyclonal
IgG and polyclonal
IgM may function to promote remyelination by different mechanisms.
IVIG may function based on its immunomodulatory activity, while the activity of
IgM is critically dependent upon its reactivity with CNS
antigens. This possibility has clear relevance to the use of
antibodies as a
therapy for
multiple sclerosis, suggesting that combined treatment with
antibodies exerting immunomodulatory activity, in concert with
antibodies that function through direct binding to CNS
antigens, may synergize to enhance the efficacy of the
therapy.