Yasin Ahmed T, Ali Eman T, Shari Falah H, Mohammed Ali N
Basrah Hospital for Women and Children, Pharmacy Department, Basrah Health Directorate, Basrah, Iraq.
Department of Clinical Laboratory Sciences, College of Pharmacy, University of Basrah, Basrah, Iraq.
J Taibah Univ Med Sci. 2024 Aug 13;19(4):885-900. doi: 10.1016/j.jtumed.2024.08.001. eCollection 2024 Aug.
The involvement of Wnt-1-induced secreted protein-1 (WISP1/CCN4) in several inflammatory reaction has recently been proposed. Nevertheless, this protein's involvement in rheumatoid arthritis (RA) remains debated. Associations between poorly diagnosed RA and several classical markers derived from demography and biochemistry have been reported.
We sought to investigate the reliability and effectiveness of serum concentrations of CCN4, vascular cell adhesion molecule-1 (VCAM-1), matrix melloprotenase-3 (MMP-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in monitoring and predicting RA and bone damage, and their correlation with RA disease course.
The study analyzed 128 patients with RA, comprising 68 newly diagnosed and 60 previously diagnosed patients, as well as 60 controls. Biomarker levels were measured with enzyme linked immuno-sorbent assays. Routine laboratory parameters such as serological, clinical, biochemical, and hematological parameters were additionally measured. Demography, anthropometry, and clinical symptom data were collected through interviews and a questionnaire. The joint disease activity score 28 (DAS28) was used to determine disease activity.
Concentrations of four biomarkers were significantly higher in the RA group than the healthy controls. Elevated biomarker concentrations were also observed in patients with high, rather than moderate or low, DAS28-ESR activity status, except for monocyte count, hematocrit (%), and urea level. Furthermore, CCN4 level positively correlated with VCAM-1, MMP-3, and GM-CSF levels, DA-S28-CRP and DAS28-ESR. The levels of three predictive markers, CCN4, VCAM-1, and MMP-3, were elevated in non-treated patients, whereas GM-CSF level showed no difference. The highest area under the curve was 73.3% for CCN4, with 93.3% sensitivity and 64.7% specificity.
Our data suggest that CCN4 can be reliably used to indicate activity and therapeutic response associated with RA, thus facilitating earlier RA diagnosis.
最近有人提出Wnt-1诱导分泌蛋白-1（WISP1/CCN4）参与多种炎症反应。然而，这种蛋白在类风湿关节炎（RA）中的作用仍存在争议。已有报道称，诊断不明确的RA与一些源自人口统计学和生物化学的经典标志物之间存在关联。
我们试图研究血清中CCN4、血管细胞黏附分子-1（VCAM-1）、基质金属蛋白酶-3（MMP-3）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的浓度在监测和预测RA及骨损伤方面的可靠性和有效性，以及它们与RA病程的相关性。
该研究分析了128例RA患者，包括68例新诊断患者和60例既往诊断患者，以及60例对照。采用酶联免疫吸附测定法测量生物标志物水平。另外还测量了常规实验室参数，如血清学、临床、生化和血液学参数。通过访谈和问卷收集人口统计学、人体测量学和临床症状数据。采用28个关节疾病活动评分（DAS28）来确定疾病活动度。
RA组中四种生物标志物的浓度显著高于健康对照组。除单核细胞计数、血细胞比容（%）和尿素水平外，在DAS28-ESR活动度高而非中度或低度的患者中也观察到生物标志物浓度升高。此外，CCN4水平与VCAM-1、MMP-3和GM-CSF水平、DA-S28-CRP和DAS28-ESR呈正相关。三种预测标志物CCN4、VCAM-1和MMP-3的水平在未治疗患者中升高，而GM-CSF水平无差异。CCN4的曲线下面积最高，为73.3%，敏感性为93.3%，特异性为64.7%。
我们的数据表明，CCN4可可靠地用于指示与RA相关的活动度和治疗反应，从而有助于早期RA诊断。
