中性粒细胞活化生物标志物谱在类风湿关节炎患者预后和监测中的应用。
A Neutrophil Activation Biomarker Panel in Prognosis and Monitoring of Patients With Rheumatoid Arthritis.
机构信息
University of Washington, Seattle.
The Polyclinic, Seattle, Washington.
出版信息
Arthritis Rheumatol. 2020 Jan;72(1):47-56. doi: 10.1002/art.41062. Epub 2019 Dec 3.
OBJECTIVE
Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are linked to inflammation and autoimmunity, including rheumatoid arthritis (RA). However, whether NETs are present in the circulation of RA patients and contribute to inflammation and disease progression has not been carefully addressed. We undertook this study to assess markers of neutrophil activation and NET formation in plasma samples, investigating whether they add clinical value in improving the determination of prognosis and monitoring in RA patients.
METHODS
Markers of neutrophil activation (calprotectin) and cell death (NETs) were analyzed, using enzyme-linked immunosorbent assay, in serum and plasma obtained from patients in 3 cross-sectional RA cohorts and sex-matched healthy controls. A longitudinal inception cohort (n = 247), seen for a median follow-up of 8 years, was used for predictive analyses.
RESULTS
Markers of neutrophil activation and cell death were increased in RA patients compared to healthy individuals (P < 0.0001). Calprotectin levels correlated with the Clinical Disease Activity Index (r = 0.53, P < 0.0001) and could be used to distinguish between patients with disease in remission and those with active disease, an observation not seen when examining C-reactive protein levels. A biomarker panel consisting of anti-citrullinated protein antibody and calprotectin could predict erosive disease (odds ratio [OR] 7.5, P < 0.0001) and joint space narrowing (OR 4.9, P = 0.001). NET levels were associated with markers of inflammation (P = 0.0002). Furthermore, NETs and a "neutrophil activation signature" biomarker panel had good predictive value in identifying patients who were developing extraarticular nodules (OR 5.6, P = 0.006).
CONCLUSION
Neutrophils undergo marked activation and cell death in RA. Neutrophil biomarkers can provide added clinical value in the monitoring and prognosis of RA patients and may allow for early preventive treatment intervention.
目的
中性粒细胞过度激活和形成中性粒细胞胞外诱捕网（NETs）与炎症和自身免疫有关，包括类风湿关节炎（RA）。然而，RA 患者的循环中是否存在 NETs 以及它们是否有助于炎症和疾病进展尚未得到仔细研究。我们进行了这项研究，以评估血浆样本中中性粒细胞活化和 NET 形成的标志物，研究它们是否能提高 RA 患者预后和监测的临床价值。
方法
使用酶联免疫吸附试验分析了来自 3 个横断面 RA 队列和性别匹配的健康对照者的血清和血浆中的中性粒细胞活化（钙卫蛋白）和细胞死亡（NETs）标志物。使用前瞻性起始队列（n = 247）进行预测分析，中位随访 8 年。
结果
与健康个体相比，RA 患者的中性粒细胞活化和细胞死亡标志物增加（P < 0.0001）。钙卫蛋白水平与临床疾病活动指数（r = 0.53，P < 0.0001）相关，可用于区分疾病缓解和活动的患者，而观察 C 反应蛋白水平则不然。由抗瓜氨酸蛋白抗体和钙卫蛋白组成的生物标志物谱可预测侵蚀性疾病（优势比[OR] 7.5，P < 0.0001）和关节间隙狭窄（OR 4.9，P = 0.001）。NET 水平与炎症标志物相关（P = 0.0002）。此外，NET 和“中性粒细胞活化标志物谱”具有良好的预测价值，可识别出发生关节外结节的患者（OR 5.6，P = 0.006）。
结论
RA 患者中性粒细胞发生明显的活化和细胞死亡。中性粒细胞标志物可在 RA 患者的监测和预后中提供附加的临床价值，并可能允许早期预防性治疗干预。
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