Dysregulated immunity and autoantibodies: Unraveling their roles in neurological disease pathogenesis

Autoantibodies, generated by B lymphocytes following the breakdown of immune tolerance, are pathological immunoglobulins that erroneously target host tissues. Substantial evidence underscores their pivotal involvement in neurological pathologies linked to immune dysregulation. Given the escalating global burden of neurological disorders as leading contributors to morbidity and mortality, elucidating the mechanistic contributions of autoantibodies to these conditions remains a research imperative. The blood-brain barrier (BBB), a critical guardian of central nervous system homeostasis, has been demonstrated in our prior work to be vulnerable to autoimmune attack—specifically, SLE-derived monoclonal autoantibodies were found to downregulate tight junction protein expression, thereby compromising BBB integrity. These findings not only advance our understanding of autoantibody-mediated neuropathology but also motivate a comprehensive reappraisal of their multifaceted roles. This review systematically examines the dual participation of autoantibodies in both autoimmune and non-autoimmune contexts, with particular emphasis on their pathogenic mechanisms in immune-associated neurological disorders. Through comparative analysis of central and peripheral nervous system pathologies, we aim to delineate novel molecular targets and establish a refined conceptual framework to guide precision diagnostics and targeted therapeutic development.