摘要目的 探讨SLE患者血浆游离DNA(cfDNA)水平与LN的相关性,分析患者血浆cfDNA升高的可能原因.方法 实验纳入了54例SLE患者和43名健康对照者.SLE患者中,37例合并有LN,26例为活动性LN患者,11例为缓解期LN患者.血浆cfDNA的测定采用Picogreen试剂盒;低密度粒细胞(LDGs)的测定采用流式细胞术.采用单因素相关及多元线性回归分析LN与cfDNA的关系并分析cfDNA升高的影响因素.结果 SLE组的cfDNA水平显著高于健康对照组[(237±40) ng/ml和(188±41) ng/ml,P＜0.01].在SLE中,LN组的cfDNA水平显著高于非LN组[(247±47) ng/ml和(214±31) ng/ml,P=0.028);而且活动性LN的cfDNA水平明显高于缓解期LN[(254±50) ng/ml和(216±29) ng/ml,P=0.035).进一步分析发现SLE患者血浆cfDNA水平与尿蛋白定量(24 h)呈正相关(r=0.350,P=0.013),与血清白蛋白(r=-0.500,P＜0.01)和内生肌酐清除率(Ccr)(r=-0.354,P=0.044)呈负相关.LDGs在SLE患者中的比例显著高于健康对照组[(8.3±12.9)％和(1.2±0.7)％,P=0.004],并且与血浆cfDNA水平呈正相关(r=0.636,P=0.002);中性粒细胞计数与cfDNA呈正相关(r=0.599,P＜0.01).结论 LDGs和中性粒细胞过度形成中性粒细胞胞外网状陷阱(NETs)是SLE患者cfDNA水平升高的主要原因之一.血浆cfDNA的水平与LN的活动性相关,提示NETs标记物和活动性LN存在联系,更特异的血清NETs标记物有望成为活动性LN的临床标志.

abstractsObjective 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.