Significance of Autoantibodies

Abstract

The field of autoimmune neurological disorders is rapidly expanding, and novel autoantibodies and their neuronal antigens continue to be discovered. Autoimmunity targeting brain proteins is enigmatic, because traditionally, the central nervous system (CNS) is viewed as immune-privileged. However, the discovery of the lymphatic and glymphatic circulation in the CNS demonstrates the interaction between the CNS and the immune response. Furthermore, the barriers protecting the brain from direct exposure to the immune response can be compromised by inflammations, infection, or injury. A compromised blood–brain barrier, or blood–cerebrospinal fluid barrier, will allow egress of neuronal antigens to regional and peripheral lymphoid organs and may lead to the initiation of an autoimmune response. Peripheral autoantibodies or intrathecally produced autoantibodies can reenter the CNS. Besides being useful diagnostic markers, these autoantibodies may be involved in the pathogenesis of the disease by mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and modulation of receptor function. The effect of a neural autoantibody depends not only on the nature of its antigen but also on the antibody’s Ig isotype or IgG subclass. We will discuss different causes of neurological autoimmunity and pathogenic mechanisms involved in neurological autoimmune diseases. Finally, we will discuss naturally occurring IgM autoantibodies and IgG4 autoantibodies with protective and reparative functions and appropriate treatment options.