Anti-N-Methyl-D-Aspartic Acid Receptor 2 (Anti-NR2) Antibody in Neuropsychiatric Lupus Serum Damages the Blood-Brain Barrier and Enters the Brain.

Abstract

BackgroundBrain microvessel endothelial cells constitute an important component in the blood-brain barrier. Cell-culture-based models of the blood-brain barrier (BBB) have been extensively applied in pharmacology, pathology and physiology. This study investigated effects of anti-N-methyl-D-aspartic acid receptor 2 (anti-NR2), N-methyl-D-aspartic acid (NMDA) receptor antibodies, NMDA receptor antagonists, and NMDA receptor agonists on brain microvessel endothelial cell models, and verified the effect of anti-NR2 antibody on the BBB as a receptor agonist.Material/MethodsThe primary brain microvessel endothelial cells were isolated and cultured, and an in vitro BBB model was established based on microvessel endothelial cells. Anti-NR2 antibody, glutamic acid, ifenprodil, and memantine were added in the BBB model to analyze changes in transepithelial electrical resistance (TEER) and to examine the permeability of the brain microvessel endothelial cell model.ResultsThe results showed that TEER values were significantly decreased by the addition of anti-NR2 antibody and glutamate, but were significantly increased by the addition of ifenprodil and memantine. TEER values showed no changes when treated by anti-NR2 antibody and ifenprodil, as well as anti-NR2 antibody and memantine. When dexamethasone was added, the TEER values increased by 23.8%, 39.4%, and 29.6% by treating with anti-NR2 antibody, positive cerebrospinal fluid, and positive serum, respectively.ConclusionsOur findings show that anti-NR2 antibody in neuropsychiatric lupus serum can damage the BBB and enter the brain.