부산대학교 도서관

A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy, patients with these neuroglial surface autoantibody (NSAb)-mediated diseases often experience clinical relapse, high rates of long-term morbidity and adverse effects from the available medications. Fundamentally, the autoantigen-specific B cell lineage leads to production of the pathogenic autoantibodies. These autoantigen-specific B cells have been consistently identified in the circulation of patients with NSAb-mediated diseases, accompanied by high serum levels of autoantigen-specific antibodies. Early evidence suggests that these cells evade well-characterized B cell tolerance checkpoints. Nearer to the site of pathology, cerebrospinal fluid from patients with NSAb-mediated diseases contains high levels of autoantigen-specific B cells that are likely to account for the intrathecal synthesis of these autoantibodies. The characteristics of their immunoglobulin genes offer insights into the underlying immunobiology. In this Review, we summarize the emerging knowledge of B cells across the NSAb-mediated diseases. We review the evidence for the relative contributions of germinal centres and long-lived plasma cells as sources of autoantibodies, discuss data that indicate migration of B cells into the CNS and summarize insights into the underlying B cell pathogenesis that are provided by therapeutic effects. A distinct set of CNS diseases are caused by autoantibodies to neuroglial surface proteins, and immunotherapy has limited ability to control these conditions in the long term. In this Review, the authors discuss in detail the B cell biology that underlies these diseases and consider the therapeutic implications. Key points Autoantigen-specific B cells that target neuroglial surface proteins are responsible for the production of pathogenic neuroglial surface autoantibodies (NSAbs) in an increasing variety of antibody-mediated CNS diseases. Pathogenic NSAbs are typically found at higher concentrations in the serum than in the cerebrospinal fluid. Current evidence suggests that autoreactive B cells evade early B cell tolerance checkpoints in NSAb-mediated CNS diseases. Enrichment of autoantigen-specific B cells in the cerebrospinal fluid in patients with NSAb-mediated diseases suggests that they migrate into this compartment and secrete pathogenic IgGs intrathecally. Experimental and clinical evidence implicates both ongoing germinal centre reactions and long-lived plasma cells in the propagation of autoantibody production in NSAb-mediated diseases.
Author(s): Bo Sun [sup.1] , Melanie Ramberger [sup.1] , Kevin C. O'Connor [sup.2] , Rachael J. M. Bashford-Rogers [sup.3] , Sarosh R. Irani [sup.1] Author Affiliations: (1) Oxford Autoimmune Neurology [...]