Friday, 10 Apr 2020

You are here

Metformin May Improve Netosis Driven Lupus Activity

Neutrophil extracellular traps (NETs) are first line defense tools used to trap microbial pathogens. These dense networks of extracellular fibers, composed of DNA from neutrophils may also be important in the pathogenesis of systemic lupus erythematosus (SLE) as they are potent activators of plasmacytoid dendritic cells (pDCs) and type I interferon (IFN) release.

Wang and coworkers studied NETs from PMA stimulated neutrophils in lupus, RA and control patients. They showed that mitochonrial DNA (mtDNA) in NETs and anti-mtDNA Abs was elevated in SLE patients compared with controls and significantly correlated with IFN scores and disease activity. Moreover, they found mitochonrial DNA in NETs found in renal biopsies of patients with lupus nephritis and that these same NETs were important inducers of plasmacytoid dendritic cell production of IFN-α.

They also examined the effects of metformin, in vitro and in a clinical trial, on down-regulating NET activity and lupus outcomes. Metformin decreased PMA-induced NET formation and pDCs IFN-ɑ generation. They also did a controlled trial of metformin or placebo in a 113 patient pilot study of metformin in patients with mild/moderate SLE patients, and showed that adjunctive metformin decreased clinical flare-up, prednisone exposure and body weight.  

These data suggest therapies targeting NET activity may be beneficial in lupus.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

In Lupus, Keep BP Below 130/80

Blood pressure should be maintained at a level below 130/80 mm Hg in all patients with lupus to lessen their likelihood of atherosclerotic vascular events, Canadian researchers asserted.

In Vasculitis, Beware of Infection

Risks of infection were strikingly high among patients with antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis, which may relate to both the disease and its treatment, Scottish researchers found.

Malignancies with Giant Cell Arteritis

The Journal of Rheumatology reports the findings of a Swedish population-based cohort study of biopsy-proven giant cell arteritis (GCA) patients showing that the overall risk for cancer was not increased; yet there appears to be an increased risk for leukemia and a decreased risk for breast and upper gastrointestinal tract cancers.   

Hospitalized GPA - Higher morbidity, Mortality and Cost

Rheumatology reports on a study of patients with granulomatosis with polyangiitis (GPA) showing worse outcomes and higher costs when hospitalized with GPA.

GPA patients were identified from the Nationwide Inpatient Sample (NIS) and were compared to those without GPA with regard to demographics, procedures, length of stay, mortality, morbidity and total hospitalization charges (between 2005–2014).

Don't Blame the Weather in Sjogren's

Seasonal variations in symptoms -- commonly reported by patients with rheumatic diseases -- were not observed in a large cohort of patients with primary Sjogren's syndrome, French investigators found.