Blood-brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus

• Published in: Autoimmunity reviews Vol. 18; no. 4; pp. 426 - 432
• Main Authors: Duarte-Delgado, Nancy P., Vásquez, Gloria, Ortiz-Reyes, Blanca L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019
• Subjects: Autoantibodies; Blood-Brain Barrier - immunology; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Blood-brain barrier and mechanisms; Cell Membrane Permeability - physiology; Complement; Cytokines; Encephalitis - complications; Encephalitis - immunology; Humans; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - immunology; Lupus Vasculitis, Central Nervous System - etiology; Lupus Vasculitis, Central Nervous System - immunology; Lupus Vasculitis, Central Nervous System - pathology; Neuroimmunomodulation - physiology; Neuropsychiatric systemic lupus erythematosus; Neuropsychiatric systemic lupus erythematosus; Complement; Autoantibodies; Cytokines; Blood-brain barrier and mechanisms
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2018.12.004

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that can involve nervous system commitment known as neuropsychiatric systemic lupus erythematosus (NPSLE). The diagnostic of NPSLE is complex because the symptoms range from focal symptoms (e.g., strokes, thrombotic events) to diffuse disorders affecting cognition, mood and level of consciousness (e.g. acute confusional state, psychosis). Both type of manifestations of NPSLE differ in their pathological mechanisms. The focus of this review will be on the mechanisms that lead to the blood-brain barrier (BBB) disruption and to the neuroinflammation related with the diffuse manifestations of NPSLE. •The breakdown of the blood brain barrier involves the direct effect of cytokines and complement proteins.•TWEAK plays an important role in BBB disruption through the induction of cytokines in endothelial cells (ECs).•The complement protein C5a promotes a cytoskeletal remodeling that destabilizes the tight and adherens junctions of ECs.•The anti-NMDAR and anti-RP antibodies are key effectors of neuronal damage by induction of apoptosis.•The diffuse manifestations of NPSLE result in increased intrathecal production of cytokines, specially IL-6