Antibody-mediated remyelination: relevance to multiple sclerosis

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.