IgG anti–NR2 glutamate receptor autoantibodies from patients with systemic lupus erythematosus activate endothelial cells
Open Access
- 10 October 2012
- journal article
- systemic lupus-erythematosus
- Published by Wiley in Arthritis & Rheumatism
- Vol. 65 (2), 457-463
- https://doi.org/10.1002/art.37745
Abstract
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.Keywords
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