Cerebrospinal fluid immunoglobulin G promotes oligodendrocyte progenitor cell migration

Multiple sclerosis (MS) is characterized by demyelination of the CNS with associated neurological deficits. Remyelination can occur but is often incomplete. The process of myelin repair requires the proliferation and migration of oligodendrocyte progenitor cells (OPC) into the lesion from the neighboring areas. OPC migration is altered by several factors, including antibodies that bind to OPC surface proteins. We have previously reported elevated anti-OSP/claudin-11 antibodies in the cerebrospinal fluid (CSF) of MS patients and that anti-OSP/claudin-11 antibodies generated in rabbits can inhibit OPC migration. In the study presented here, we investigated the effect of CSF IgG from MS patients and controls on OPC migration in culture. Rat OPC cultured with CSF from MS patients tended to migrate more than those cultured with control CSF, but this did not reach statistical significance. To determine whether the IgG fraction in the CSF influenced migration, we removed it using protein-A sepharose. A dramatic decrease in OPC migration was found in both MS (45 +/- 24 vs.16 +/- 9) and control (40 +/- 19 vs. 22 +/- 13) samples after IgG was removed (P <.05). Anti-OSP/claudin-11 antibody concentration did not significantly correlate with OPC migration. These data demonstrate that CSF IgG promotes OPC migration. Identification of the specific IgG fraction responsible for this effect could lead to novel therapies to promote recovery in MS.