Levels of Circulating Cell-free DNA Could Help Determine Lupus Activity, Study Suggests

Levels of Circulating Cell-free DNA Could Help Determine Lupus Activity, Study Suggests

Levels of circulating cell-free DNA can potentially be used as a biomarker for assessing disease activity and monitoring treatment effectiveness in patients with systemic lupus erythematosus (SLE), a study shows.

The study, “High levels of circulating cell free DNA are a biomarker of active SLE,” was published in the European Journal of Clinical Investigation.

SLE, a chronic, inflammatory autoimmune disorder, affects the skin, joints, kidneys, and other organs. One of the characteristics of SLE is the increased release of DNA — which is normally housed inside the cells — to the outside environment.

Over time, most patients develop autoantibodies against the extracellular DNA, which are known to participate in the disease mechanisms that contribute to the development of SLE.

Highly fragmented genomic DNA is a normal component of blood plasma. Studies on circulating plasma cell-free DNA (cfDNA) have shown the cfDNA usually originates from the death of white blood cells.

Recent studies, however, have shown that SLE patients have higher levels of circulating cfDNA than healthy individuals.

Based on these studies, researchers have become interested in potentially using cfDNA levels as a marker for disease activity and response to treatment.

Therefore, researchers set out to examine the relationship between cfDNA levels and disease activity in SLE patients. In particular, they focused on pregnant SLE patients with active disease because they are more prone to adverse reproductive and obstetric outcomes.

Researchers recruited 58 women with SLE, 36 of whom were pregnant and 22 who were not. Levels of their cfDNA were compared with those of matching healthy controls, including 199 who were pregnant and 60 who were not with no history of SLE.

The median levels of cfDNA were significantly higher in nonpregnant SLE patients, at 7.38 ng/ml, and pregnant SLE patients, at 7.65 ng/ml, than in nonpregnant (4.6 ng/ml) and pregnant healthy controls (5.25 ng/ml).

Importantly, using SLE disease activity index (SLEDAI) scores, researchers showed that the median cfDNA levels were significantly higher in patients with active disease than in those with inactive disease.

While there was a trend of increased cfDNA levels with higher SLEDAI scores, researchers found no association between high cfDNA levels and nephritis (inflammation of the kidney), skin manifestations, multi-organ inflammations, or other inflammatory markers.

Researchers believe this might be due to limitations of the study, such as “the small comparative sample size, the degree and severity of the inflammations (which was not measured quantitatively) and the effects of the different drug regimens used to dampen inflammation.”

“Our findings showed that higher levels of cfDNA levels are present in the circulation of SLE patients and that elevated levels correlate with higher SLEDAI scores,” the investigators concluded. “We propose that a simple cfDNA assay may have useful clinical utility as an additional diagnostic tool to monitor disease activity, help guide treatment and better assist the clinician in the management of SLE patients.”

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