Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29010 Málaga, Spain.
UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain.
Int J Mol Sci. 2023 Apr 5;24(7):6800. doi: 10.3390/ijms24076800.
This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case-control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR ( = 0.032) and HAQ values ( = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17-5.22]; = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24-6.78]; = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00-1.12]; = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00-1.06]; = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00-1.00]; = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07-1.46]; = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.
本研究旨在鉴定炎症因子和可溶性细胞因子,这些因子可作为类风湿关节炎相关间质性肺病(RA-ILD)诊断和预后的生物标志物。我们对 RA-ILD 患者进行了嵌套前瞻性病例对照研究,这些患者按性别、年龄和 RA 诊断后时间进行匹配。所有参与者均接受了肺功能测试和高分辨率计算机断层扫描。ILD 根据美国胸科学会/欧洲呼吸学会的标准定义;肺疾病的进展定义为 FVC 恶化> 10%或 DLCO 恶化> 15%。炎症相关变量包括使用 DAS28-ESR 和多重细胞因子测定法测量的炎症活性。运行了两个 Cox 回归模型来确定与 ILD 和 ILD 进展相关的因素。研究人群包括 70 名患者:35 名 RA-ILD 患者(病例)和 35 名无 ILD 的 RA 患者(对照)。更多的病例具有更高的 DAS28-ESR(= 0.032)和 HAQ 值(= 0.003)。Cox 回归分析中与 RA-ILD 相关的变量是疾病活动度(DAS28)(HR [95% CI],2.47 [1.17-5.22];= 0.017)和高水平的 ACPA(HR [95% CI],2.90 [1.24-6.78];= 0.014),pg/mL 中的 IL-18(HR [95% CI],1.06 [1.00-1.12];= 0.044),pg/mL 中的 MCP-1/CCL2(HR [95% CI],1.03 [1.00-1.06];= 0.049)和 pg/mL 中的 SDF-1(HR [95% CI],1.00 [1.00-1.00];= 0.010)。唯一与 ILD 进展相关的变量是 pg/mL 中的 IL-18(HR [95% CI],1.25 [1.07-1.46];= 0.004)。我们的数据支持 RA-ILD 患者的炎症活性高于无 ILD 的 RA 患者。一些细胞因子与 RA-ILD 患者的诊断和预后较差均相关。