DNA-bound proteins from NETs predict worse kidney outcomes

Higher Elastase-DNA, HMGB1-DNA levels mean full remission 2X as unlikely

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by Margarida Maia |

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DNA-bound proteins released from traps cast by neutrophils, a type of immune cell, may help predict which lupus nephritis patients are most likely to respond to treatment two years after a renal (kidney) flare, a study indicates.

Those with higher levels of Elastase-DNA and HMGB1-DNA were more than twice as likely to not achieve complete remission, where all symptoms have resolved. They also were more likely to develop severe kidney disease.

“The levels of neutrophil extracellular [outside the cell] trap remnants measured at the time of a renal flare may help identify patients at high risk of worse renal outcomes,” the researchers wrote in “Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis,” which was published in Lupus Science & Medicine.

Lupus occurs when immune cells mistakenly attack healthy tissues, resulting in inflammation. When inflammation hits the kidneys, which is what happens in lupus nephritis, they can stop working properly.

Neutrophils quickly travel to sites of infection or injury where they cast lacy structures called NETs to entrap bacteria or other foreign particles. These NETs are made up of stretches of DNA coiled around proteins.  The speed at which they act may come at a price, though. The immune response is so strong and unspecific that it must be well controlled to prevent it from damaging the body. Neutrophils appear to be more likely to form NETs with lupus.

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 Predicting kidney outcomes with lupus

Here, researchers in Canada measured the levels of certain DNA-bound proteins released from NETs in the bloodstream during a renal flare to find out if they could predict kidney outcomes over two years.

The study included 72 adults with lupus (49 with active, 23 with inactive disease) and 20 healthy people. The levels of Elastase-DNA and HMGB1-DNA were significantly higher in lupus patients. The DNA-bound proteins also tended to be higher in those with active disease, among whom the levels were significantly higher in those with lupus nephritis.

The researchers analyzed a second group of 109 adults with active lupus nephritis. Most (84.4%) were women and were a median age of 29. Over a third (37.6%) went into complete remission at 12 months. At 24 months, the proportion was higher, 51.4%.

Those with proliferative lupus nephritis had significantly higher levels of Elastase-DNA and HMGB1-DNA than those with nonproliferative lupus nephritis. Proliferative lupus nephritis is linked to a higher risk of end-stage kidney disease, where the kidneys stop working.

People with higher levels of Elastase-DNA were 2.34 times more likely to not achieve complete remission two years after a kidney flare. Those with higher HMGB1-DNA had even higher odds — 2.61 times.

The findings were similar regarding the odds of progressing to severe kidney disease. People with higher levels of Elastase-DNA were 2.84 times more likely to have worse outcomes. The odds about doubled for those with higher HMGB1-DNA.

The researchers said Elastase-DNA and HMGB1-DNA may “serve as predictors of adverse renal outcomes, including response to therapy and decline in kidney function.”

Besides providing information about the link between NETs and lupus, “measurement of NET remnants could serve as a biomarker to identify patients at a high risk for poor outcomes,” they wrote.