狼疮性肾炎患者血清NETs、TWEAK、外周血CD4^(+)T/CD8^(+)T比例与疾病活动度及肾脏预后的关系

Relationship between Serum NETs,TWEAK,Peripheral Blood CD4^(+)T/CD8^(+)T Ratio and Disease Activity and Renal Prognosis in Patients with Lupus Nephritis

目的:探讨狼疮性肾炎(LN)患者血清中性粒细胞胞外诱捕网(NETs)、肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)、外周血分化簇(CD)4^(+)T/CD8^(+)T比例与疾病活动度及肾脏预后的关系。方法:选取2021年8月~2022年8月川北医学院附属医院肾内科收治的LN患者137例(LN组),根据系统性红斑狼疮疾病活动指数(SLEDAI)-2000评分分为轻度活动组(52例)、中度活动组(45例)、重度活动组(40例)。随访1年,根据肾脏相关终点事件发生情况分为预后不良组(43例)和预后良好组(94例),另选取同期76名体检健康志愿者(对照组)。采用酶联免疫吸附法检测血清NETs、TWEAK水平,流式细胞术检测外周血CD4^(+)T/CD8^(+)T比例。Spearman相关性分析LN患者血清NETs、TWEAK和外周血CD4^(+)T/CD8^(+)T与SLEDAI-2000评分的相关性,多因素Logistic回归分析LN患者预后不良的因素,受试者工作特征曲线分析血清NETs、TWEAK和外周血CD4^(+)T/CD8^(+)T对LN患者预后不良的预测价值。结果:与对照组比较,LN组血清NETs、TWEAK水平升高,外周血CD4^(+)T/CD8^(+)T降低(P<0.05)。轻度活动组、中度活动组、重度活动组血清NETs、TWEAK依次升高,外周血CD4^(+)T/CD8^(+)T依次降低(P<0.05)。LN患者SLEDAI-2000评分与血清NETs、TWEAK呈正相关,与外周血CD4^(+)T/CD8^(+)T呈负相关(P<0.05)。慢性肾脏病分期4期、SLEDAI-2000评分升高、NETs升高、TWEAK升高为LN患者预后不良的独立危险因素,估算肾小球滤过率升高、CD4^(+)T/CD8^(+)T升高为独立保护因素(P<0.05)。血清NETs、TWEAK和外周血CD4^(+)T/CD8^(+)T联合预测LN患者预后不良的曲线下面积为0.943,大于血清NETs、TWEAK和外周血CD4^(+)T/CD8^(+)T单独预测的0.790、0.788、0.799(P<0.05)。结论:LN患者血清NETs、TWEAK水平升高,外周血CD4^(+)T/CD8^(+)T降低,与疾病活动度及肾脏预后不良密切相关,血清NETs、TWEAK联合外周血CD4^(+)T/CD8^(+)T预测LN患者肾脏预后的价值较高。

Objective:To investigate the relationship between serum neutrophil extracellular traps(NETs),tumor necrosis factorlike weak inducer of apoptosis(TWEAK),peripheral blood cluster of differentiation(CD)4^(+)T/CD8^(+)T ratio and disease activity and renal prognosis in patients with lupus nephritis(LN).Methods:137 LN patients(LN group)who were admitted to the Department of Nephrology,Affiliated Hospital of North Sichuan Medical College from August 2021 to August 2022 were selected,patients were divided into mild activity group(52 cases),moderate activity group(45 cases)and severe activity group(40 cases)according to the systemic lupus erythematosus disease activity index(SLEDAI)-2000 score.After 1 years of follow-up,patients were divided into poor prognosis group(43 cases)and good prognosis group(94 cases)according to the occurrence of kidney-related endpoint events,another 76 healthy volunteers(control group)were selected during the same period.The levels of serum NETs and TWEAK were detected by enzyme-linked immunosorbent assay,and the proportion of CD4^(+)T/CD8^(+)T in peripheral blood was detected by flow cytometry.The correlation between serum NETs,TWEAK,peripheral blood CD4^(+)T/CD8^(+)T and SLEDAI-2000 score in LN patients were analyzed by Spearman correlation analysis,the factors of poor prognosis in LN patients were analyzed by multivariate Logistic regression analysis,the predictive value of serum NETs,TWEAK and peripheral blood CD4^(+)T/CD8^(+)T for poor prognosis in LN patients were analyzed by receiver operating characteristic curve.Results:Compared with control group,the levels of serum NETs and TWEAK in LN group were increased,and the peripheral blood CD4^(+)T/CD8^(+)T was decreased(P<0.05).The serum NETs and TWEAK in mild activity group,moderate activity group and se-vere activity group increased in turn,and the peripheral blood CD4^(+)T/CD8^(+)T decreased in turn(P<0.05).SLEDAI-2000 score in LN patients was positively correlated with serum NETs and TWEAK,and negatively correlated with peripheral blood CD4^(+)T/CD8^(+)T(P<0.05).Chronic kidney disease stage 4,elevated SLEDAI-2000 score,elevated NETs and elevated TWEAK were independent risk factors for poor prognosis in LN patients,increased estimated glomerular filtration rate and elevated CD4^(+)T/CD8^(+)T were independent protective factors(P<0.05).The area under the curve of serum NETs,TWEAK and peripheral blood CD4^(+)T/CD8^(+)T combined to predict poor prognosis in LN patients was 0.943,which was greater than 0.790,0.788 and 0.799 predicted by serum NETs,TWEAK and peripheral blood CD4^(+)T/CD8^(+)T alone(P<0.05).Conclusions:The levels of serum NETs and TWEAK in LN patients are increase,and the peripheral blood CD4^(+)T/CD8^(+)T is decrease,which are closely relate to disease activity and poor renal prognosis,serum NETs and TWEAK combine with peripheral blood CD4^(+)T/CD8^(+)T has a high value in predicting renal prognosis in LN patients.