血清CX3CL1、CCL17与类风湿关节炎相关间质性肺疾病患者肺功能及预后的关系研究

A study on the relationship between serum CX3CL1,CCL17 and lung function and prognosis in patients with rheumatoid arthritis associated interstitial lung disease

目的分析血清C-X3-C基序趋化因子配体1(CX3CL1)、C-C基序趋化因子配体17(CCL17)与类风湿关节炎相关间质性肺疾病(RA-ILD)患者肺功能及预后的关系。方法选取2017年1月—2018年1月上海中医药大学附属龙华医院风湿科收治RA患者295例,根据是否合并ILD分为ILD组115例和非ILD组180例,根据预后情况将RA-ILD患者分为预后不良亚组和预后良好亚组。检测血清CX3CL1、CCL17水平及肺功能指标[第1秒用力呼气容积(FEV_(1))、用力肺活量(FVC)、FEV_(1)/FVC和肺一氧化碳弥散量(DLCO)]。采用Pearson相关性分析RA-ILD患者血清CX3CL1、CCL17水平与肺功能指标的相关性,多因素Logistic回归分析RA-ILD患者预后不良的影响因素,受试者工作特征(ROC)曲线分析血清CX3CL1、CCL17水平预测RA-ILD患者预后不良的价值。结果与非ILD组比较,ILD组血清CX3CL1、CCL17水平升高,FEV_(1)、FVC、FEV_(1)/FVC、DLCO降低(t/P=14.359/<0.001、13.855/<0.001、12.015/<0.001、2.732/0.007、14.749/<0.001、14.010/<0.001)。Pearson相关性分析显示,RA-ILD患者血清CX3CL1、CCL17水平与FEV_(1)、FVC、FEV_(1)/FVC、DLCO呈负相关(r=-0.762、-0.711、-0.577、-0.534、-0.707、-0.692、-0.735、-0.672,P均<0.001)。随访5年,115例RA-ILD患者预后不良发生率为46.96%。多因素Logistic回归分析显示,普通型间质性肺炎和高分辨率电子计算机断层扫描(HRCT)评分、CX3CL1、CCL17升高为RA-ILD患者预后不良的独立危险因素[OR(95%CI)=3.745(1.245~11.264)、1.051(1.008~1.095)、1.008(1.003~1.012)、1.037(1.012~1.062)],FEV_(1)、FEV_(1)/FVC、DLCO升高为独立保护因素[OR(95%CI)=0.952(0.896~0.988)、0.892(0.867~0.981)、0.857(0.789~0.949)]。ROC曲线分析显示,血清CX3CL1、CCL17水平联合预测RA-ILD患者预后不良的曲线下面积为0.875,大于CX3CL1、CCL17单独预测的0.783、0.788(Z=2.807、2.698,P=0.005、0.007)。结论RA-ILD患者血清CX3CL1、CCL17水平升高,与肺功能降低和预后不良有关,血清CX3CL1、CCL17水平联合检测对RA-ILD患者预后具有较高的预测价值。

Objective To analyze the relationship between serum C-X3-C motif chemokine ligand 1(CX3CL1)and C-C motif chemokine ligand 17(CCL17)with lung function and prognosis in patients with rheumatoid arthritis associated interstitial lung disease(RA-ILD).Methods 295 RA patients admitted to the Rheumatology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2017 to January 2018 were selected.They were divided into ILD group(115 cases)and non ILD group(180 cases)based on the presence of ILD.RA-ILD patients were divided into poor prognosis subgroup and good prognosis subgroup based on their prognosis.Detect serum levels of CX3CL1 and CCL17,as well as lung function indicators[forced expiratory volume at 1 second(FEV_(1)),forced vital capacity(FVC),FEV_(1)/FVC,and lung carbon monoxide diffusion(DLCO)].Pearson correlation analysis was used to examine the correlation between serum CX3CL1 and CCL17 levels and lung function indicators in RA-ILD patients.Multivariate logistic regression analysis was used to identify the factors influencing poor prognosis in RA-ILD patients.Receiver Operating Characteristic(ROC)curve analysis was used to assess the value of serum CX3CL1 and CCL17 levels in predicting poor prognosis in RA-ILD patients.Results Compared with the non ILD group,the serum levels of CX3CL1 and CCL17 in the ILD group increased,while FEV_(1),FVC,FEV_(1)/FVC,and DLCO decreased(t/P=14.359/<0.001,13.855/<0.001,12.015/<0.001,2.732/0.007,14.749/<0.001,14.010/<0.001).Pearson correlation analysis showed that serum CX3CL1 and CCL17 levels in RA-ILD patients were negatively correlated with FEV_(1),FVC,FEV_(1)/FVC,and DLCO(r=-0.762,-0.711,-0.577,-0.534,-0.707,-0.692,-0.735,-0.672,all P<0.001).During a 5-year follow-up,the incidence of poor prognosis in 115 RA-ILD patients was 46.96%.Multivariate logistic regression analysis showed that common type interstitial pneumonia,high-resolution computed tomography(HRCT)score,CX3CL1,and elevated CCL17 were independent risk factors for poor prognosis in RA-ILD patients[OR(95%CI)=3.745(1.245-11.264),1.051(1.008-1.095),1.008(1.003-1.012),1.037(1.012-1.062)],FEV_(1),FEV_(1)/FVC Elevated DLCO is an independent protective factor[OR(95%CI)=0.952(0.896-0.988),0.892(0.867-0.981),0.857(0.789-0.949)].ROC curve analysis showed that the area under the curve for predicting poor prognosis in RA-ILD patients with serum CX3CL1 and CCL17 levels combined was 0.875,which was greater than the 0.783 and 0.788 predicted by CX3CL1 and CCL17 alone(Z=2.807,2.698,P=0.005,0.007).Conclusion Elevated serum levels of CX3CL1 and CCL17 in RA-ILD patients are associated with decreased lung function and poor prognosis.The combined detection of serum levels of CX3CL1 and CCL17 has high predictive value for the prognosis of RA-ILD patients.