Axonal injury is considered the major cause of chronic disability in multiple sclerosis (MS) patients, however the mechanisms behind remain still unclear. Recently, it was demonstrated that autoantibodies against Neurofascin, a cell adhesion molecule within the adult nervous system, can contribute to the development of axonal pathology in some patients. We compared the ability of the two different isoforms of Neurofascin, Nfasc155 and Nfasc186, to induce a pathogenic antibody response in the Dark Agouti (DA) rat. Animals were immunized with recombinant proteins prior to induction of experimental autoimmune encephalomyelitis (EAE) by adoptive transfer of activated MOG-specific T cells. Only Nfasc186 induced an axopathic autoantibody response in vivo, despite extensive cross reactivity between the two isoforms as shown by ELISA and flow cytometry.
There has been much focus of myelin antigens such as myelin oligodendrocyte glycoprotien as a site for damaging antibodies. However when the blood of MSers is looked at you never find every one with antibodies to any one protein. However this true of virtually all target proteins. However that is not to say that they are not important. In this study they look at Neurofascin. These molecules are important in the axon and myelin interface around the Nodes of Ranvier (the gap between myelin that helps nerve impuslses travel quicker). There are two variants (see picture) and antibodies against the bigger of the two 186Kda verses 155Kda (a da = dalton which is an indicate of the size of the molecule) cause nerve damage in they get into the brain. This is another way that problems are caused in MSers.