Two of four studied autoantibodies against double-stranded DNA activated NF-kB and TNF production
High levels of different auto-antibodies are commonly found in lupus, as well as other autoimmune disease. One type of auto-antibody is directed against double-stranded DNA.
In the study below, researchers looked at four variations of that auto-antibody and found that all four resulted in an increase in TNF – a pro-inflammatory mediator.
Two of the four variants were found to activate NF-kB, suggesting that at least some of the damage caused by these auto-antibodies results from their ability to turn on NF-kB.
This is a very significant finding, and furthers the theory that inhibition of NF-kB might be of value in lupus, as well as other autoimmune disease.
The publication:
[stextbox id="grey"]
Immunol Lett. 2009 Jun 4;124(2):70-6. Epub 2009 Apr 24.
Mouse monoclonal autoantibodies penetrate mouse macrophage cells and stimulate NF-kappaB activation and TNF-alpha release.
Jang EJ, Nahm DH, Jang YJ.
Summary of the abstract
Autoantibodies against double-stranded DNA (dsDNA) are found in the serum of systemic lupus erythematosus (SLE) patients. However, the mechanism by which anti-dsDNA antibodies (Abs) contribute to the pathogenesis of SLE is not yet fully understood.
In this study, we investigated four anti-dsDNA mouse monoclonal autoantibodies that share positively charged amino acids (including arginines) in their complementarity determining regions for their ability to penetrate RAW264.7 macrophage cells, activate NF-kappaB and stimulate TNF-alpha production.
All four antibodies penetrated into macrophage cells and increased the level of extracellular TNF-alpha.
Two also activated NF-kappaB.
The fact that two of four cell-penetrating anti-dsDNA mAbs induced both NF-kappaB activation and TNF-alpha production in macrophages suggests that at least some autoantibodies against dsDNA may play a role in the pathogenesis of SLE by penetrating into macrophage cells and nuclei, and subsequently inducing the pro-inflammatory cytokine, TNF-alpha, by binding to the NF-kappaB gene and stimulating its transcriptional activity.
[/stextbox]