Pathogenic mechanisms of autoantibodies in neurological autoimmune diseases

Over recent decades, the significance of autoantibodies has been increasingly recognized in neurological diseases. Breakthroughs, such as the identification of pathogenic autoantibodies targeting aquaporin-4 in central nervous system demyelinating disorders and N-methyl-D-aspartate receptors in autoimmune encephalitis, have revolutionized both the discovery and mechanistic investigation of autoantibodies in neurological diseases. Methodological advances, particularly the utilization of patient-derived monoclonal autoantibodies and cryogenic electron microscopy, have enabled the precise characterization of pathogenic human autoantibodies. In this review, we recapitulate the pathogenic mechanisms of autoantibodies in neurological autoimmune diseases. Furthermore, we propose a classification framework for autoantibodies based on their pathogenic hierarchies. This review aims to advance conceptual paradigms and inspire future mechanistic studies of autoantibodies in neurological diseases.