Autoantibodies and their potential roles in diseases of the nervous system

Autoantibodies are found in many disorders of the nervous system, including diseases affecting the peripheral nervous system (e.g. Guillain–Barré syndrome and other peripheral neuropathies), the central nervous system (e.g. neuromyelitis optica, multiple sclerosis and limbic encephalitis) and the neuromuscular junction (e.g. myasthenia gravis), as well as in neuropsychiatric disorders and in paraneoplastic syndromes. Some of these antibodies are likely to play an important pathogenic role in disease development, whereas others might be useful biomarkers for disease. In the present review, the features of an autoantibody that enable it to be pathogenic (e.g. the antibody isotype and the target antigen against which the antibody is directed) and some of the different mechanisms by which pathogenic autoantibodies could act will be discussed. These mechanisms include antibody‐mediated cell lysis, opsonization of target proteins for attack by macrophages, cross‐linking of Fc receptors, blocking or destroying receptors involved in neurotransmission or cellular homeostasis, and blocking of repair mechanisms such as remyelination. Examples will be given of diseases where these antibody‐mediated mechanisms are known or thought to be active. Finally, approaches to treating autoantibody‐mediated disease in the nervous system will be briefly reviewed.