IgG Anti-NR2 Glutamate Receptor Autoantibodies From Patients With Systemic Lupus Erythematosus Activate Endothelial Cells

Objective. To investigate the possibility that IgG anti-NR2 glutamate receptor antibodies (anti-NR2) derived from patients with systemic lupus erythematosus (SLE) cause an immunologic interaction with endothelial cells (ECs) in the blood-brain barrier, resulting in inflammation of the blood-brain barrier, allowing the entrance of these autoantibodies into the cerebrospinal fluid. Methods. Purified IgG anti-NR2 antibodies from 14 patients with SLE were tested for their ability to bind to double-stranded DNA (dsDNA) and ECs, to modulate endothelial adhesion molecule expression and cytokine production by ECs, and to activate the NF-kappa B pathways in the ECs. Purified IgG from 5 normal subjects was used as a negative control. Results. Purified IgG anti-NR2 antibodies bound to dsDNA in an IgG-dose-dependent manner. This interaction up-regulated the expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 on the EC surface and increased the production of interleukin-6 (IL-6) and IL-8, but not tumor necrosis factor alpha or IL-1 beta, by ECs. Purified IgG anti-NR2 also activated the degradation of cytoplasmic I kappa B, indicating the activation of NF-kappa B in the ECs. Conclusion. EC activation through the NF-kappa B signaling pathway induced by IgG anti-NR2 antibodies in the central nervous system of SLE patients may lead to inflammation of the blood-brain barrier, initiating the pathogenesis of neuropsychiatric SLE.