COMMENTARY

Casting a 'NET' to Find New Therapies for Lupus

Kevin Deane, MD, PhD

Disclosures

March 02, 2016

Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin

Wang H, Li T, Chen S, Gu 1, Ye S
Arthritis Rheumatol. 2015;67:3190-3200

Article Summary

Part of how neutrophils function to mediate inflammation and fight infection is by producing neutrophil extracellular traps (NETs) that are extruded from the cells when the cell is stimulated. These NETs contain several components, including antimicrobial peptides, nuclear material, and other pattern recognition receptors, that can interact with Toll-like receptors to stimulate the innate immune system.[1] Emerging data support the idea that NETs also play an important role in a variety of autoimmune diseases, including lupus.[2]

Building on this, as reported in their article published in the December 2015 issue of Arthritis and Rheumatology, Wang and colleagues found that NETs containing mitochondrial DNA (mtDNA) were present in patients with active lupus. They also found that antibodies to mtDNA were elevated in patients with lupus and were associated with nephritis. Furthermore, they found that mtDNA was deposited in NETs in nephritic renal biopsy specimens, and that a combination of mtDNA and anti-mtDNA antibodies was a more potent inducer of interferon (a leading inflammatory cytokine in lupus) relative to double-stranded DNA (dsDNA) and anti-dsDNA antibodies.

Finally, in a small clinical trial presented in the same article, the investigators found that the use of metformin, a drug known to have antioxidant properties and known to inhibit mitochondrial respiratory burst, led to improved clinical variables when added to other therapies in patients with mild to moderate lupus.

Viewpoint

The field of rheumatology has been relatively stagnant for years in terms of introducing new therapies for lupus, although the approval of the drug belimumab was a welcome change. It is exciting that Wang and colleagues have built upon knowledge of the role of NETs in lupus to identify a potentially new therapeutic option for lupus. It is still at an early stage, but we should look forward to progress in our understanding of NETs in autoimmune disease and the potential to target NETs for treatment.

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