One of our recent posts on “metabolic disturbances in SLE” reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment. (The Global Innovations – metabolic-disturbances-associated-with-systemic-lupus-erythematosus).
The current study states that: A candidate source of autoantigen is the neutrophil extracellular trap (NET), which releases nucleic acids into the extracellular environment, generating a structure composed of DNA coated with antimicrobial proteins. On the basis of in vitro and patient correlative studies, several groups have suggested that NETs may provide lupus autoantigens.
The observation that NET release (NETosis) relies on activity of the phagocyte NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox2) in neutrophils of both humans and mice provided a genetic strategy to test this hypothesis in vivo. Therefore, an X-linked nox2 null allele was crossed onto the lupus-prone MRL.Faslpr genetic background and assessed immune activation, autoantibody generation, and SLE pathology.
Counter to the prevailing hypothesis, Nox2-deficient lupus-prone mice had markedly exacerbated lupus, including increased spleen weight, increased renal disease, and elevated and altered autoantibody profiles. Moreover, heterozygous female mice, which have Nox2 deficiency in 50% of neutrophils, also had exacerbated lupus and altered autoantibody patterns, suggesting that failure to undergo normal Nox2-dependent cell death may result in release of immunogenic self-constituents that stimulate lupus.
These results indicate that NETosis does not contribute to SLE in vivo; instead, Nox2 acts to inhibit disease pathogenesis, making this enzyme an important target for further study and a candidate for therapeutic intervention.
- Metabolic Disturbances Associated with Systemic Lupus Erythematosus
- Lupus Patients May Benefit From Vitamin D Supplements (medicalnewstoday.com)
- Coupon Savings For the Month (jenlynn401.wordpress.com)
- Vitamin D supplements may benefit lupus patients (medicalxpress.com)
- A surprise mechanism uncovered in the development of lupus (news.yale.edu)
- Malar rash (en.wikipedia.org)
- Belimumab for lupus erythematosus: Added benefit not proven (medicalxpress.com)
- Lupus – it’s a part of me. (thelupylady.com)
- Vitamin D supplements may benefit lupus patients (eurekalert.org)
- Belimumab for lupus erythematosus: Added benefit not proven (eurekalert.org)