近日,内蒙古医科大学附属医院检验科郑文琪课题组闫志老师,使用IPHASE品牌产品:CD4+T 细胞在《Cytokine》期刊上发表文章《Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion》,影响因子3.8!
本论文中,评估了 CXCL9 和 CXCL11 对结核性胸腔积液(TPE)的诊断潜力,并确定了它们在 TPE 发生过程中的细胞起源和作用。我们在中国的两个中心前瞻性地招募了未确诊的胸腔积液患者。我们收集了入院时的胸腔积液,并测定了 CXCL9 和 CXCL11 的水平。采用 ROC 曲线和 DCA 评估了 CXCL9 和 CXCL11 的诊断准确性。用卡介苗(Bacillus Calmette-Guérin,BCG)处理 THP-1 细胞衍生的巨噬细胞,并采用 qRT-PCR 和 ELISA 方法测定 CXCL9 和 CXCL11。CXCL9和CXCL11对Th细胞的趋化吸引活性通过透孔试验进行了分析。我们发现胸膜 CXCL9 和 CXCL11 是 TPE 的潜在诊断标志物,但其诊断准确性在老年患者中受到影响。CXCL9 和 CXCL11 可促进外周 Th 细胞向胸膜腔迁移,从而成为治疗 TPE 的靶点。
摘要
Background: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic
accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE.
Methods: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating character-istic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Gu´erin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay.
Results: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55–0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92–1.00) and 0.97 (95 % CI: 0.94–1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. Conclusions: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.
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