Pathogenic and physiological autoantibodies in the central nervous system

In this article, we review the current knowledge on pathological and physiological autoantibodies directed toward structures in the central nervous system (CNS) with an emphasis on their regulation and origin. Pathological autoantibodies in the CNS that are associated with autoimmunity often lead to severe neurological deficits via inflammatory processes such as encephalitis. In some instances, however, autoantibodies function as a marker for diagnostic purposes without contributing to the pathological process and/or disease progression. The existence of naturally occurring physiological autoantibodies has been known for a long time, and their role in maintaining homeostasis is well established. Within the brain, naturally occurring autoantibodies targeting aggregated proteins have been detected and might be promising candidates for new therapeutic approaches for neurodegenerative disorders. Further evidence has demonstrated the existence of naturally occurring antibodies targeting antigens on neurons and oligodendrocytes that promote axonal outgrowth and remyelination. The numerous actions of physiological autoantibodies as well as their regulation and origin are summarized in this review.