The Role of Autoimmunity in Multiple Sclerosis

Abstract

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), is one of the most common neurological diseases of young adults in developed countries. Hallmarks of this disease are focal plaques of demyelination in the white matter of the CNS. Evidence for autoimmune processes in this disease is mostly circumstantial. First, autoreactive T cells are found in the blood of most patients. This by itself does not yet point to a role of these cells in the disease process, since CNS antigen–specific T cells are also normal components in the immune system of healthy individuals. However, experiments in animal models of autoimmune encephalomyelitis clearly demonstrated that such cells can initiate CNS inflammation once they are activated. Second, autoreactive T cells and antibodies have been found in MS lesions, and immunotherapies targeting CNS antigen–specific T cells may delay or ameliorate the disease progression in MS patients. However, the situation is much more complex. To date, no MS specific autoimmune response has been described. The triggers, which might set off or maintain autoimmunity in a chronic disease course lasting years or decades, remain unknown. Autoimmune responses in the CNS of MS patients are not invariably detrimental, but may even be beneficial. Finally, diffuse alterations indicating general neurodegenerative processes are present throughout the brain of many MS patients, and these alterations are not necessarily due to immunemediated mechanisms. Hence, there are still many gaps to fill in the “autoimmune hypothesis” of MS.