Department of Rheumatology and Immunology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Department of Rheumatology and Immunology, Shanghai Tongji Hospital, Shanghai, China.
Inflammation. 2022 Aug;45(4):1800-1814. doi: 10.1007/s10753-022-01661-w. Epub 2022 Mar 22.
Previous studies have suggested a correlation between uric acid (UA) and lung lesion in some diseases. However, it remains unknown whether UA contributes to the lung injury in rheumatoid arthritis (RA). Our study aimed to investigate the clinical value of the UA level in the severity of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We measured UA in serum and bronchoalveolar lavage fluid (BALF), and UA levels of subjects were compared. As for the role of UA on ILD, we incubated A549 cells with UA and the expression of EMT markers was measured by immunofluorescence staining. The concentrations and messenger RNA expression of IL-1, IL-6, and transforming growth factor-β (TGF-β) were measured by ELISA and RT-PCR, respectively. We observed that serum UA levels in RA were significantly higher than those in controls. And, higher UA was measured in both serum and BALF of patients with RA-ILD, particularly those with interstitial pneumonia (UIP) pattern. Additionally, the correlation of the serum and BALF UA levels with serum KL-6, a biomarker of ILDs, in RA was significant (r = 0.44, p < 0.01; r = 0.43, p < 0.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity (r = -0.61, p < 0.01; r = -0.34, p < 0.01) and diffusing capacity for carbon monoxide (r = -0.43, p < 0.01; r = -0.30, p < 0.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69-0.80; p < 0.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78-0.91; p < 0.01), which showed the significance of the UA in clinical settings. Also, the in vitro experiment showed that UA induced epithelial-to-mesenchymal transition (EMT) and production of IL-1, IL-6, and TGF-β in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.
先前的研究表明，在某些疾病中尿酸（UA）与肺部病变之间存在相关性。然而，UA 是否导致类风湿关节炎（RA）中的肺损伤仍不清楚。我们的研究旨在探讨 UA 水平在类风湿关节炎相关间质性肺病（RA-ILD）严重程度中的临床价值。我们测量了血清和支气管肺泡灌洗液（BALF）中的 UA 水平，并比较了受试者的 UA 水平。至于 UA 对ILD 的作用，我们用 UA 孵育 A549 细胞，并通过免疫荧光染色测量 EMT 标志物的表达。通过 ELISA 和 RT-PCR 分别测量白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和转化生长因子-β（TGF-β）的浓度和信使 RNA 表达。我们观察到 RA 患者的血清 UA 水平明显高于对照组。并且，RA-ILD 患者的血清和 BALF 中均测量到较高的 UA，尤其是间质性肺炎（UIP）模式的患者。此外，RA 患者血清和 BALF UA 水平与血清 KL-6（ILD 的生物标志物）之间的相关性具有统计学意义（r=0.44，p<0.01；r=0.43，p<0.01）。并且，在患者中，血清和 BALF 中 UA 的水平与用力肺活量（r=-0.61，p<0.01；r=-0.34，p<0.01）和一氧化碳弥散量（r=-0.43，p<0.01；r=-0.30，p<0.01）呈负相关。在 ROC 曲线分析中，UA 对 RA-ILD 的 AUC 值为 0.744（95%CI：0.69-0.80；p<0.01），血清 UA 对预测 RA-ILD 患者 UIP 模式的 AUC 值为 0.845（95%CI：0.78-0.91；p<0.01），这表明 UA 在临床环境中的重要性。此外，体外实验表明 UA 诱导 A549 细胞上皮-间充质转化（EMT）和白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和转化生长因子-β（TGF-β）的产生。因此，UA 水平升高可能是 RA-ILD 的诊断标志物，特别是 RA-UIP。
