Liu Lu, de Leeuw Karina, van Goor Harry, Doornbos-van der Meer Berber, Arends Suzanne, Westra Johanna
Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen, 9700 RB, The Netherlands.
Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands.
Arthritis Res Ther. 2024 Dec 19;26(1):220. doi: 10.1186/s13075-024-03454-y.
To investigate the levels of plasma neutrophil extracellular traps (NETs) and free thiols, the latter reflecting systemic oxidative stress (OS), and to explore the relationship between NETs and OS in quiescent systemic lupus erythematosus (SLE) patients with and without renal involvement.
Plasma levels of NETs and free thiols were measured cross-sectionally in 100 SLE patients with low disease activity (SLEDAI < 5), of whom 73 patients had no renal involvement (non-LN) and 27 patients had lupus nephritis (LN). Additionally, 22 healthy controls (HCs) were included. NETs were measured using a myeloperoxidase-DNA complex ELISA and free thiols were measured using a thiol assay kit.
NETs levels were significantly higher in both non-LN and LN patients compared to HCs (p < 0.001, p = 0.013), with no difference between the two patient groups (p = 0.799). Free thiol levels were not significantly different between groups. Interestingly, NETs were negatively correlated with free thiols in all 100 SLE patients (rho = -0.32) and non-LN patients (rho = -0.38), but not in LN patients. Levels of free thiols were significantly lower in subgroups of patients with estimated glomerular filtration rate (eGFR) < 60, serum creatinine (sCr) ≥ 90, C reactive protein (CRP) levels ≥ 5 and body mass index (BMI) ≥ 30. In multivariable regression, disease duration, NETs levels, and eGFR were independently associated with free thiol levels.
Levels of NETs were increased in quiescent SLE patients. Although free thiol levels did not differ among the groups. The levels of NETs and free thiols were independently associated in SLE patients, suggesting a potential role of OS in NETs formation. Therefore, reducing OS might be an additional therapeutic target for SLE treatment.
研究血浆中性粒细胞胞外陷阱（NETs）和游离巯基水平，后者反映全身氧化应激（OS），并探讨NETs与OS在有肾累及和无肾累及的静止期系统性红斑狼疮（SLE）患者中的关系。
对100例疾病活动度低（SLEDAI＜5）的SLE患者进行横断面研究，测定其血浆NETs和游离巯基水平，其中73例患者无肾累及（非狼疮性肾炎，non-LN），27例患者有狼疮性肾炎（LN）。另外纳入22名健康对照者（HCs）。采用髓过氧化物酶-DNA复合物酶联免疫吸附测定法检测NETs，采用巯基检测试剂盒检测游离巯基。
与HCs相比，non-LN和LN患者的NETs水平均显著升高（p＜0.001，p = 0.013），两组患者之间无差异（p = 0.799）。各组间游离巯基水平无显著差异。有趣的是，在所有100例SLE患者（rho = -0.32）和non-LN患者（rho = -0.38）中，NETs与游离巯基呈负相关，但在LN患者中无此相关性。在估计肾小球滤过率（eGFR）＜60、血清肌酐（sCr）≥90、C反应蛋白（CRP）水平≥5和体重指数（BMI）≥30的患者亚组中，游离巯基水平显著较低。在多变量回归分析中，病程、NETs水平和eGFR与游离巯基水平独立相关。
静止期SLE患者的NETs水平升高。尽管各组间游离巯基水平无差异。NETs水平与游离巯基水平在SLE患者中独立相关，提示OS在NETs形成中可能起作用。因此，减轻OS可能是SLE治疗的另一个治疗靶点。
