Recent advances in the pathogenesis of neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a highly heterogeneous and clinically challenging manifestation of systemic lupus erythematosus, encompassing a broad spectrum of diffuse and focal neuropsychiatric symptoms. Conventional models have emphasized vascular injury and blood-brain barrier (BBB) dysfunction; however, these frameworks alone do not fully account for phenotypic diversity, frequent absence of overt structural lesions, or variable associations with systemic disease activity.

This review summarizes recent advances in the understanding of immune cell infiltration, resident central nervous system (CNS) cell responses, cytokine and chemokine networks, autoantibody-mediated effects, and CNS barrier-related mechanisms in NPSLE. We discuss how interactions among barrier systems, microglial activation, astrocytic reactivity, neuronal vulnerability, and context-dependent autoantibody effects collectively shape CNS pathology. Relevant literature was identified through searches of the PubMed database for studies published up to January 2026 focusing on neuroimmune mechanisms, cytokine networks, CNS barrier dysfunction, and autoantibody-mediated neuronal injury in NPSLE.

Integrating these processes within a neuroimmune framework highlights the importance of barrier-associated mechanisms in linking systemic autoimmunity to CNS-specific disease. This perspective supports mechanism-informed stratification and may inform future diagnostic approaches and targeted therapeutic strategies in NPSLE.