medwireNews: Analysis suggests that plasma levels of neutrophil extracellular traps (NETs) – markers of neutrophil cell death – in patients with systemic lupus erythematosus (SLE) may identify those at risk for increased disease activity and severe comorbidities.
These findings “could provide opportunities for preventive treatment and/or closer monitoring of patients at high risk of flare,” say the researchers.
They analyzed plasma NET levels in a total of 370 SLE patients from four cross-sectional cohorts and found that these SLE patients had significantly elevated levels of NETs, with levels above the 99th percentile upper limit for 100 healthy controls.
Christian Lood, from the University of Washington in Seattle, USA, and co-investigators note that NET levels “surprisingly” did not correlate with disease activity at the time of measurement – at which point patients had been in remission for an average of 6 months and had low disease activity.
"The occurrence of neutrophil activation and cell death even at low disease activity is intriguing, and suggests that current treatment strategies, while reducing clinical symptoms, may not be sufficient to prevent low-grade chronic inflammation and subsequent organ damage,” say Lood and study co-authors.
Increased NET levels did, however, correlate with worsening disease activity within the next 3 months. Among patients with elevated NET levels at baseline, the average SLEDAI score at 3 months was approximately 2, compared with 0 among patients with normal NET levels at baseline.
This “provides insight into the pathogenesis of SLE, suggesting that NET formation may be an early event, occurring prior to apparent clinical disease. As such, NET formation may be an ideal therapeutic target, inhibiting disease at an early stage,” the team suggests.
Indeed, using data collected on 47 SLE individuals from a fifth longitudinal cohort, the researchers found that with every 1 U/mL increase in baseline plasma NET level, the risk for disease activity worsening within the next 3 months increased by 75%, and persisted for up to a year.
The researchers comment that, not only did “NET levels reflect a propensity of SLE patients to develop a high SLEDAI,” they were also more prominent in patients with a severe disease phenotype, notably those with a history of nephritis and cardiovascular disease.
High NET levels at baseline were associated with arterial, but not venous, events and increased endothelial damage, report Lood et al in The Journal of Rheumatology, adding that “[f]urther studies are warranted to study [the] potential predictive value of NETs in the development of cardiovascular disease.”
The investigators conclude: “NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, which may allow for early interventions.”
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