Antibody-Mediated Mechanisms in Autoimmune Neurological Disorders

Antibody-mediated encephalitides are a rapidly evolving class of disorders in which autoantibodies against neuronal surface proteins disrupt synaptic function, neural circuits and cognition. This article summarizes the presentations and discussions from a symposium at the 2025 meeting of the Spanish Society of Neuroscience (SENC). Rather than providing a comprehensive review of autoimmune encephalitis, we highlight selected advances that illustrate how antibody-mediated mechanisms contribute to neurological dysfunction, using anti-NMDAR encephalitis as a paradigmatic example. Specifically, we contrast experimental approaches that have shaped current understanding of disease pathogenesis, including in vitro systems, passive-transfer mouse models and active immunization paradigms that capture B-cell responses, intrathecal immunity, microglial engagement and relapse biology. We also examine emerging evidence that antibody Fc features, including subclass and glycosylation, contribute to innate immune activation and clinical heterogeneity, with examples linking proinflammatory Fc signatures to poorer outcomes. Finally, we review selected studies addressing behavioural and cognitive consequences in animal models and patients, particularly long-lasting deficits in working memory, and discuss therapeutic implications ranging from synapse-stabilizing strategies and NMDAR positive allosteric modulators to B-cell-targeting treatments and approaches aimed at modulating Fc-dependent pathways. Together, these findings suggest that integrating molecular immunoprofiling with systems neuroscience may improve prognostic accuracy and inform therapies that restore immune homeostasis and functional circuit recovery.