Elevated plasma level of circulating cell-free DNA may derive from NETosis and is associated with active lupus nephritis in systemic lupus erythematosus / 中华风湿病学杂志

ABSTRACT

Objective To explore the correlations between elevated cfDNA with lupus nephritis and indentify the influencing factors of cfDNA in systemic lupus erythematosus (SLE).Methods Fifty four patients with SLE [37 patients with lupus nephritis (LN) and 43 age-and sex-matched healthy controls] were included in the study.In 37 LN patients,26 patients were at active stage,and 11 patients were in remission.cfDNA concentration was measured with Picogreen Kit and low-density granulocytes (LDGs) was tested by flowcytometer.Correlation and regression analysis were performed to discover whether cfDNA is related to LN and identify the influencing factor of cffDNA.Results The cfDNA in SLE group was (237±40) ng/ml,which was significantly higher than that in healthy control group (188±41 ng/ml,P＜0.01).cfDNA in LN group was significantly higher than that in patients without LN (NLN) (247±47 ng/ml vs 214±31 ng/ml,P=0.028).cfDNA in patients with active LN was significantly higher than that in patient with inactive LN (RLN) (254±50 ng/ml vs 216±29 ng/ml,P=0.035).In SLE group,cfDNA was positively correlated with quantitative 24-hour urinary protein (r=0.350,P=0.013) and reversely correlated with albumin (r=-0.500,P＜0.01) and endogenous creatinine clearance rate (Ccr) (r=-0.354,P=0.044).Percentage of LDGs in peripheral blood mononuclear ceils (PBMCs) of the SLE group was (8.3± 12.9)％,significantly was higher than that in healthy controls [(1.2±0.7)％,P=0.004].The cfDNA was positively correlated with LDGs (r=0.636,P=0.002) and neutrophils (r=0.599,P＜0.01).Conclusion NETs excessively released by neutrophils as well as LDGs may be one of the main reasons for elevated cfDNA level in SLE.cfDNA level is associated with LN activity,suggesting that there is a intrinsic link between NETs-related biomarkers and active LN and that more specific biomarkers of NETs may become a clinical biomarker for active LN.