摘要
目的:检测CXC趋化因子配体10(CXC motif chemokine 10,CXCL-10)和涎液化糖链抗原6(Krebs von den lungen-6,KL-6)在类风湿关节炎合并肺间质病变(rheumatoid arthritis associated interstitial lung disease,RA-ILD)患者血清中的表达水平,分析其与RA-ILD的相关性,探讨CXCL-10和KL-6对RA-ILD患者病情评价的意义.方法:选择2021年5月至2023年10月在北京市顺义区医院风湿免疫科住院及门诊治疗的169例类风湿关节炎(rheu-matoid arthritis,RA)患者的病例资料进行回顾性分析,根据是否合并ILD分为RA-ILD组82例和RA-non-ILD组87例,根据入排标准最终筛选出两组各80例.采用酶联免疫吸附试验检测所有患者血清CXCL-10和KL-6水平,通过1:1倾向性评分匹配法(propensity score matching,PSM)对两组患者进行匹配,得到组间协变量均衡的样本.比较匹配后的组间差异,分析血清CXCL-10、KL-6与ILD评分(Warrick评分)、临床实验室及肺功能参数之间的相关性,利用二元Logistic回归分析RA患者发生ILD的危险因素,并判断CXCL-10、KL-6对RA-ILD的预测价值.结果:经1:1 PSM匹配出RA-ILD组和RA-non-ILD组患者各49例.RA-ILD组血清CXCL-10、KL-6水平显著高于RA-non-ILD 组[CXCL-10 水平 64.36(34.01,110.18)ng/L vs.29.80(16.89,40.55)ng/L,P＜0.001;KL-6 水平360.70(236.35,715.05)U/mL vs.210.69(159.98,255.50)U/mL,P＜0.001].RA-ILD 患者血清 CXCL-10 水平与Warrick评分呈正相关(r=0.378,P=0.007),与用力肺活量(forced vital capacity,FVC)占正常预计值的百分比(FVC％)呈负相关(r=-0.338,P=0.018);KL-6 与类风湿因子(rheumatoid factor,RF)呈正相关(r=0.296,P=0.039),与 FVC％(r=-0.436,P=0.002)和一氧化碳弥散量(diffusion lung carbon monoxide,DLCO)占预计值的百分比(DLCO％,r=-0.426,P=0.002)呈负相关.单因素和多因素二元Logistic回归分析均提示CXCL-10(OR值分别为1.035、1.023,P均＜0.05)、KL-6水平(OR值分别为1.004、1.005,P均＜0.05)与ILD呈正相关.分别用CXCL-10和KL-6绘制ROC曲线,曲线下面积分别为0.770和0.752,联合检测曲线下面积可增加至0.800.结论:RA-ILD患者血清CXCL-10和KL-6水平明显升高,与ILD患者ILD严重程度有一定的相关性,两者联合检测对诊断RA-ILD有较高的参考价值.
Abstract
Objective:To detect the serum level of chemokine CXC motif chemokine 10(CXCL-10)and Krebs von den lungen-6(KL-6)in patients with rheumatoid arthritis associated interstitial lung dis-ease(RA-ILD),and to analyze their correlation with RA-ILD,as well as the significance in RA-ILD.Methods:A total of 169 RA patients were enrolled in the study.According to imaging findings of with and without ILD in high-resolution computed tomography scans of chest,the subjects were divided into RA-ILD group and RA-non-ILD group.According to the inclusion and exclusion criteria,80 patients in each of the two groups were finally selected.Two groups were matched according to the 1:1 ratio using propensity score matching(PSM).The serum CXCL-10 and KL-6 levels were detected by enzyme-linked immunosorbent assay.The clinical features,laboratory data and medications between the two groups were compared after PSM and the correlation between serum levels and clinical parameters were analyzed.Bi-nary Logistic regression was used to analyze the risk factors of ILD in the RA patients,and the predictive value of CXCL-10 and KL-6 in RA-ILD was evaluated.Results:In this study,49 patients with RA-ILD and 49 patients with RA-non-ILD were selected by PSM.The levels of CXCL-10 and KL-6 in the RA-ILD group[64.36(34.01,110.18)ng/L,360.70(236.35,715.05)U/mL]were significantly higher than those in the RA-non-ILD group[29.80(16.89,40.55)ng/L,210.69(159.98,255.50)U/mL](all P＜0.001).The results of correlation analysis showed that the level of serum CXCL-10 was positively correlated with the Warrick score on chest CT(r=0.378,P=0.007)and negatively correlated with the percentage of forced vital capacity to the predicted value(FVC％,r=-0.338,P=0.018).And the level of KL-6 was positively correlated with rheumatoid factor(RF,r=0.296,P=0.039)and nega-tively correlated with FVC％(r=-0.436,P=0.002)and the percentage of diffusion capacity for car-bon monoxide to the predicted value(DLCO％,r=-0.426,P=0.002).Both univariate and multiva-riate Logistic regression analysis showed that CXCL-10 and KL-6 were positively correlated with ILD,the values of OR were 1.035 and 1.023 in CXCL-10 and those were 1.004 and 1.005 in KL-6 respectively(P＜0.05).The ROC curves were plotted with CXCL-10 and KL-6.The area under the curve(AUC)was 0.770 and 0.752 respectively.The AUC of combined detection increased to 0.800.Conclusion:Serum levels of CXCL-10 and KL-6 are significantly elevated in patients with RA-ILD and correlated with the severity of ILD.The combined estimate of them helps to improve the effectiveness of diagnosis.
万方数据