特发性膜性肾病患者血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值与免疫抑制剂治疗疗效的关系分析

Analysis of the Relationship between Serum APRIL,MCP-1,CD4^(+)/CD8^(+)Ratio and Immunosuppressive Therapy Efficacy in Patients with Idiopathic Membranous Nephropathy

目的:探讨特发性膜性肾病(IMN)患者血清增殖诱导配体(APRIL)、单核细胞趋化蛋白1(MCP-1)、CD4^(+)/CD8^(+)比值与免疫抑制剂治疗疗效的关系。方法:选择2020年1月~2022年3月在南华大学附属娄底医院接受免疫抑制剂治疗的IMN患者167例为研究对象。采用酶联免疫吸附法(ELISA)检测治疗前血清APRIL、MCP-1水平,采用流式细胞仪检测CD4^(+)、CD8^(+),计算CD4^(+)/CD8^(+)比值。治疗结束后根据疗效分为有效组(n=126)和无效组(n=41),比较两组血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值。采用Logistics回归模型分析IMN免疫抑制剂治疗疗效的影响因素,采用受试者工作特征(ROC)曲线分析血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值对免疫抑制剂治疗无效的预测价值。结果:无效组血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值均高于有效组(P<0.05)。单因素分析结果显示,IMN患者免疫抑制剂治疗疗效与病理分期、24 h尿蛋白、血肌酐(Scr)、胱抑素C(Cys C)、肾小球滤过率(GFR)有关(P<0.05);多因素Logistics回归分析显示,血清APRI、MCP-1、CD4^(+)/CD8^(+)比值升高及病理分期为III、IV期是IMN免疫抑制剂治疗无效的独立危险因素(P<0.05)。血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值及联合检测预测IMN患者免疫抑制剂治疗无效的曲线下面积(AUC)分别为0.815、0.811、0.749和0.939,三项联合检测的预测价值优于各指标单独检测。结论:血清APRIL、MCP-1、CD4^(+)/CD8^(+)比值升高均是IMN免疫抑制剂治疗无效的独立危险因素,三项指标联合检测对IMN免疫抑制剂治疗疗效具有较高的预测价值。

Objective:To investigate the relationship between serum aproliferation inducing ligand(APRIL),monocyte chemoattractant protein-1(MCP-1),CD4^(+)/CD8^(+)ratio and immunosuppressive therapy efficacy in patients with idiopathic membranous nephropathy(IMN).Methods:167 IMN patients who received immunosuppressive therapy in Loudi Hospital Affiliated to South China University from January 2020 to March 2022 were selected as the research objects.The levels of serum APRIL and MCP-1 before treatment were detected by enzyme-linked immunosorbent assay(ELISA),CD4^(+)and CD8^(+)were detected by flow cytometry,and the ratio of CD4^(+)/CD8^(+)was calculated.Patients were divided into effective group(n=126)and ineffective group(n=41)according to the curative effect after treatment,the serum APRIL,MCP-1 and CD4^(+)/CD8^(+)ratio were compared between two groups.The influencing factors of the efficacy of immunosuppressive therapy for IMN were analyzed by Logistic regression model,the predictive value of serum APRIL,MCP-1 and CD4^(+)/CD8^(+)ratio for ineffective immunosuppressive therapy was analyzed by receiver operating characteristic(ROC)curve.Results:The serum APRIL,MCP-1 and CD4^(+)/CD8^(+)ratio in ineffective group were higher than those in effective group(P<0.05).Univariate analysis showed that,the efficacy of immunosuppressive therapy in IMN patients was related to pathological stage,24 h urine protein,serum creatinine(Scr),cystatin C(CysC),and glomerular filtration rate(GFR)(P<0.05).Multivariate Logistic regression analysis showed that,elevated serum APRI,MCP-1,CD4^(+)/CD8^(+)ratio and pathological stage III and IV were independent risk factors for ineffective immunosuppressive therapy for IMN(P<0.05).The area under the curve(AUC)of serum APRIL,MCP-1,CD4^(+)/CD8^(+)ratio and combined detection for predicting ineffective immunosuppressive therapy in IMN patients were 0.815,0.811,0.749 and 0.939 respectively,the predictive value of combined detection was better than that of each index alone.Conclusion:The increase of serum APRIL,MCP-1 and CD4^(+)/CD8^(+)ratio are independent risk factors for the ineffective treatment of IMN immunosuppressive agents,the combine detection of the three indicators has a high predictive value for the efficacy of IMN immunosuppressive agents.