血清CHI3L1、Clusterin对类风湿关节炎活动度及治疗反应性的预测价值分析

Predictive value of serum CHI3L1 and Clusterin in rheumatoid arthritis activity and treatment responsiveness

目的探讨血清壳多糖酶3样蛋白1(CHI3L1)、簇集蛋白(Clusterin)对类风湿关节炎活动度及治疗反应性的预测价值。方法选取2019年7月至2021年7月上海中医药大学附属第七人民医院收治的107例类风湿关节炎患者作为研究对象,所有患者均接受甲氨蝶呤联合依那西普治疗,根据治疗半年后反应性,分为反应良好组(84例)和无反应组(23例)。采用酶联免疫吸附试验检测患者治疗前后血清CHI3L1、Clusterin水平。应用Pearson相关分析探讨血清CHI3L1、Clusterin与类风湿关节炎疾病活动度的关系,受试者工作特征(ROC)曲线评估血清CHI3L1、Clusterin对类风湿关节炎患者治疗反应性的预测价值,多因素Logistic回归分析探讨影响类风湿关节炎患者治疗反应性的相关因素。结果与无反应组比较,反应良好组关节压痛指数<14%、关节肿胀指数<6.4%的患者比例更高,治疗前后28处关节疾病活动度评估(DAS28)评分更低(P<0.05)。两组患者治疗后血清CHI3L1、Clusterin水平均降低,且与无反应组比较,反应良好组血清CHI3L1、Clusterin水平更低(P<0.05)。Pearson相关分析显示,类风湿关节炎患者治疗前后血清CHI3L1、Clusterin与DAS28评分均呈正相关(r=0.403、0.452、0.541、0.627,均P<0.05)。ROC曲线结果显示,治疗后血清CHI3L1、Clusterin预测类风湿关节炎患者治疗反应性的曲线下面积(AUC)分别为0.832、0.769,最佳截断值分别为69.85 ng/mL、44.39μg/mL,特异度分别为69.05%、52.38%,灵敏度分别为91.30%、91.30%,二者联合预测的AUC为0.921,特异度为86.90%,灵敏度为86.95%。多因素Logistic回归分析结果显示,关节压痛指数≥14%、关节肿胀指数≥6.4%、CHI3L1高表达、Clusterin高表达是影响类风湿关节炎患者治疗反应性的危险因素(P<0.05)。结论血清CHI3L1、Clusterin与类风湿关节炎患者的疾病活动度呈正相关,且二者能够作为预测治疗反应性的生物学指标,有临床推广的价值。

Objective To investigate the predictive value of serum chitinase 3-like protein 1(CHI3L1)and clusterin(Clusterin)in rheumatoid arthritis activity and treatment response.Methods A total of 107 patients with rheumatoid arthritis who were treated in Seventh People′s Hospital of Shanghai University of Traditional Chinese Medicine from July 2019 to July 2021 were selected as the research subjects.All patients received methotrexate combined with etanercept.According to the response after half a year of treatment,they were divided into the good response group(84 cases)and the non-response group(23 cases).Serum CHI3L1 and Clusterin levels were detected by enzyme-linked immunosorbent assay before and after treatment.Pearson correlation analysis was used to investigate the relationship between serum CHI3L1,Clusterin and disease activity of rheumatoid arthritis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum CHI3L1 and Clusterin on the treatment response of patients with rheumatoid arthritis.Multivariate Logistic Regression analysis was used to explore the related factors affecting the response to treatment in patients with rheumatoid arthritis.Results Compared with the non-response group,the rate of joint tenderness index<14%and joint swelling index<6.4%in the good response group were higher,and the DAS28 score before and after treatment was lower(P<0.05).The serum CHI3L1 and Clusterin levels in the two groups of patients after treatment were decreased,and compared with the non-response group,the serum CHI3L1 and Clusterin levels in the good response group were lower(P<0.05).The results of Pearson correlation analysis showed that serum CHI3L1,Clusterin were positively correlated with DAS28 scores in patients with rheumatoid arthritis before and after treatment(r=0.403,0.452,0.541,0.627,both P<0.05).The results of the ROC curve showed that the area under the curve(AUC)of serum CHI3L1 and Clusterin after treatment for predicting the treatment response of rheumatoid arthritis patients were 0.832 and 0.769,respectively,the cut-off values were 69.85 ng/mL and 44.39μg/mL,and the specificities were 69.05%and 52.38%,respectively.The sensitivities were 91.30%and 91.30%,respectively.The AUC of the combined prediction was 0.921,the specificity was 86.90%,and the sensitivity was 86.95%.Multivariate Logistic regression analysis showed that joint tenderness index≥14%,joint swelling index≥6.4%,high expression of CHI3L1,and high expression of Clusterin were the risk factors for treatment response in patients with rheumatoid arthritis(P<0.05).Conclusion Serum CHI3L1 and Clusterin are positively correlated with disease activity in patients with rheumatoid arthritis,and they could be used as biological indicators to predict response to treatment,and have clinical value.