Zeng Yanli, Xu Wenlong, Chao Pengli, Xiao Yun, Yang Tianci
Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease,School of Medicine,XiamenUniversity, Xiamen 361004, China; Xiamen Clinical Laboratory Quality ControlCenter,Zhongshan Hospital Xiamen University, Xiamen 361004, China.
Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China.
Int Immunopharmacol. 2025 Jan 27;146:113840. doi: 10.1016/j.intimp.2024.113840. Epub 2024 Dec 16.
The heterogeneity of systemic lupus erythematosus (SLE) poses a significant challenge in identifying biomarkers for assessing disease activity. Currently, there is a paucity of established biomarkers capable of evaluating SLE flares. This study aimed to identify novel biomarkers that exhibit improved diagnostic accuracy in assessing SLE activity.
A cross-sectional study was conducted at Zhongshan Hospital Xiamen University from August 2021 to April 2024,enrolling 118 patients with SLE, including 81 cases of active SLE, 50 cases of active lupus nephritis (LN) and 30 cases of active non-LN. The objective was to evaluate the diagnostic accuracy of novel biomarker called Neutrophil Extracellular Traps(NETs) for SLE activity and analyze its correlations with conventional biomarkers such as complement C3, C4, and anti-dsDNA.
Serum NETs levels were significantly elevated in patients with active SLE and active LN(P < 0.001). Furthermore, positive correlations were observed between NETs levels and disease activity score based on Systemic Lupus Erythematosus Disease Activity Index-2 K (SLEDAI-2 K) (r = 0.64, P < 0.001), as well as anti-dsDNA antibody (r = 0.54, P < 0.001).Conversely, the NETs levels were negativity correlated with complement C3 concentration (r = -0.50, P < 0.001), as well as C4 concentration (r = -0.34,P < 0.001). Univariate and multivariate analysis revealed two biomarkers performed statistical significance: NETs (OR = 6.802, 95 %CI: 2.414-19.167,P < 0.001) and anti-dsDN A(OR = 3.95,95 %CI:1.582-9.864, P = 0.003). NETs had the highest AUC of 0.82(P < 0.001), with a cut-off at 515.47 ng/L demonstrating 61.63 % sensitivity and 96.87 % specificity. For the active LN group, the AUC was found to be 0.97 (P < 0.001), with a cutoff value of 515.47 ng/L, sensitivity of 100 %, and specificity of 59.76 %. Moreover, the active non-LN group had AUC of 0.70 (P = 0.007), with the same cutoff value, sensitivity of 89.61 %, and specificity of 51.61 %.
In contrast to conventional laboratory markers, serum NETs represent a novel diagnostic marker for assessing disease activity in SLE, demonstrating promising potential for clinical application.
系统性红斑狼疮(SLE)的异质性给识别用于评估疾病活动的生物标志物带来了重大挑战。目前,缺乏能够评估SLE病情发作的成熟生物标志物。本研究旨在识别在评估SLE活动方面具有更高诊断准确性的新型生物标志物。
2021年8月至2024年4月在厦门大学附属中山医院进行了一项横断面研究,纳入118例SLE患者,包括81例活动期SLE、50例活动期狼疮性肾炎(LN)和30例活动期非LN。目的是评估一种名为中性粒细胞胞外陷阱(NETs)的新型生物标志物对SLE活动的诊断准确性,并分析其与补体C3、C4和抗双链DNA等传统生物标志物的相关性。
活动期SLE和活动期LN患者的血清NETs水平显著升高(P<0.001)。此外,NETs水平与基于系统性红斑狼疮疾病活动指数-2K(SLEDAI-2K)的疾病活动评分之间存在正相关(r = 0.64,P<0.001),与抗双链DNA抗体也呈正相关(r = 0.54,P<0.001)。相反,NETs水平与补体C3浓度呈负相关(r = -0.50,P<0.001),与C4浓度也呈负相关(r = -0.34,P<0.001)。单因素和多因素分析显示有两种生物标志物具有统计学意义:NETs(OR = 6.802,95%CI:2.414 - 19.167,P<0.001)和抗双链DNA(OR = 3.95,95%CI:1.582 - 9.864,P = 0.003)。NETs的曲线下面积(AUC)最高,为0.82(P<0.001),截断值为515.47 ng/L时,敏感性为61.63%,特异性为96.87%。对于活动期LN组,AUC为0.97(P<0.001),截断值为515.47 ng/L,敏感性为100%,特异性为59.76%。此外,活动期非LN组的AUC为0.70(P = 0.007),截断值相同,敏感性为89.61%,特异性为51.61%。
与传统实验室指标相比,血清NETs是评估SLE疾病活动的一种新型诊断标志物,具有良好的临床应用潜力。