IgG anti-NR2 glutamate receptor autoantibodies from patients with systemic lupus erythematosus activate endothelial cells

Arthritis Rheum. 2013 Feb;65(2):457-63. doi: 10.1002/art.37745.


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-κB 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 α or IL-1β, by ECs. Purified IgG anti-NR2 also activated the degradation of cytoplasmic IκB, indicating the activation of NF-κB in the ECs.

Conclusion: EC activation through the NF-κB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / immunology*
  • Autoantibodies / pharmacology
  • Blood-Brain Barrier / immunology
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA / immunology
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology*
  • Endothelial Cells / metabolism
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Receptors, IgG / immunology
  • Receptors, N-Methyl-D-Aspartate / immunology*
  • Up-Regulation / immunology


  • Autoantibodies
  • Cytokines
  • NR2A NMDA receptor
  • Receptors, IgG
  • Receptors, N-Methyl-D-Aspartate
  • DNA