Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Autoimmune T cells are critical for the pathogenesis of MS, but pathogenic roles for autoantibodies in MS are less clear. We have found that about 40% of MS patients have elevated levels (compared to healthy controls and patients with other neurological diseases) of autoantibodies specific for the second extracellular loop of myelin proteolipid protein (PLP), the most abundant CNS myelin protein. Recently, it has been found that PLP interacts with integrins on the surface of oligodendrocyte precursor cells (OPCs) to allow migration of the OPCs. Migration of OPCs to sites of CNS demyelination is critical for subsequent remyelination of nerve fibres and resolution of attacks of disease in MS.  

The aim of the current study was to investigate whether the anti-PLP antibodies present in sera from MS patients had any effects on remyelination in vivo. Demyelination of the corpus callosum was induced by feeding cuprizone to mice for 6 weeks. Once feeding ceases, spontaneous remyelination of the corpus callosum normally occurs within 3 weeks. Purified IgG from controls, IgG from MS patients with high levels of anti-PLP antibody, or MS patient IgG from which all PLP-specific antibodies had been removed, was injected into mice from the 5^th week of cuprizone feeding for 3 weeks. Brains of mice were assessed by diffusion tensor imaging (DTI) at weeks 0, 5 and 9, and by histological assessment (following the last scan). Mice receiving IgG containing anti-PLP antibody, but not mice treated with the other IgG fractions, showed significantly reduced levels of remyelination in the corpus callosum. These findings show that anti-PLP antibodies could potentially inhibit remyelination in MS, and suggest that specifically depleting anti-PLP antibodies (e.g. by immunoabsorption apheresis) might be clinically indicated in patients with these autoantibodies.