Lu Fen-Ying, Huang Xia, Zhang Ke, Yin Xin, Lv Yang, Du Yue-Chen, Zhou Qian, Min Jing-Yu, Cheng Cui-E
Department of Gastroenterology, Affiliated Changshu Hospital of Nantong University (Changshu No. 2 People's Hospital), Changshu, People's Republic of China.
J Inflamm Res. 2025 Jun 17;18:7867-7877. doi: 10.2147/JIR.S519545. eCollection 2025.
Current challenges in inflammatory bowel disease (IBD) treatment include the invasive nature of endoscopic evaluation, the gold standard for diagnosis, and the limited prognostic value of traditional inflammatory markers such as CRP and IL-6. This study aimed to explore the potential role of neutrophil extracellular traps (NETs) as biomarkers for the diagnosis, disease monitoring, and prognosis of IBD.
A total of 100 patients with Crohn's disease or ulcerative colitis and 100 healthy controls were recruited between June 2020 and September 2022. Clinical and laboratory data were collected, and patients with inactive IBD were followed for two years to assess factors influencing disease relapse.
Significant differences were observed in the levels of NETs markers and inflammatory cytokines among the three groups. Cell-free DNA (cfDNA), myeloperoxidase (MPO)-DNA complexes, and citrullinated histone 3 (CitH3) levels were significantly elevated in the active IBD group compared to the inactive IBD and healthy control groups (P < 0.001). Additionally, inflammatory cytokines such as C-reactive protein (CRP), vascular endothelial growth factor (VEGF), IL-1β, and IL-6 were also higher in the active IBD group (P < 0.001). A positive correlation was observed between circulating NETs markers and inflammatory cytokines. Multivariate analysis identified cfDNA (OR = 1.045), MPO-DNA (OR = 1.084), and CitH3 (OR = 2.871) as independent risk factors for IBD. Furthermore, patients with higher NETs scores experienced more frequent relapses. At the 1-year follow-up, the high-NETs group had 13 relapses compared to 5 in the low-NETs group (P = 0.026), and at the 2-year follow-up, 22 versus 14 relapses (P = 0.044).
These findings suggest that NETs biomarkers may serve as effective diagnostic and prognostic tools for IBD, enabling early intervention and improved long-term management.
炎症性肠病（IBD）治疗目前面临的挑战包括作为诊断金标准的内镜评估具有侵入性，以及传统炎症标志物如CRP和IL-6的预后价值有限。本研究旨在探讨中性粒细胞胞外陷阱（NETs）作为IBD诊断、疾病监测和预后生物标志物的潜在作用。
在2020年6月至2022年9月期间招募了100例克罗恩病或溃疡性结肠炎患者和100名健康对照者。收集临床和实验室数据，对非活动性IBD患者进行两年随访，以评估影响疾病复发的因素。
三组之间在NETs标志物和炎症细胞因子水平上观察到显著差异。与非活动性IBD组和健康对照组相比，活动性IBD组的游离DNA（cfDNA）、髓过氧化物酶（MPO）-DNA复合物和瓜氨酸化组蛋白3（CitH3）水平显著升高（P<0.001）。此外，活动性IBD组中的炎症细胞因子如C反应蛋白（CRP）、血管内皮生长因子（VEGF）、IL-1β和IL-6也更高（P<0.001）。循环NETs标志物与炎症细胞因子之间存在正相关。多变量分析确定cfDNA（OR=1.045）、MPO-DNA（OR=1.084）和CitH3（OR=2.871）为IBD的独立危险因素。此外，NETs评分较高的患者复发更频繁。在1年随访时，高NETs组有13次复发，而低NETs组有5次复发（P=0.026）；在2年随访时，分别为22次和14次复发（P=0.044）。
这些发现表明，NETs生物标志物可能作为IBD有效的诊断和预后工具，实现早期干预并改善长期管理。
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