IL-33/ST2比值与红斑狼疮肾脏慢性损伤严重程度的相关性研究

摘要

AIM:To elucidate the association between chronic kidney injury and interleukin-33 (IL-33;an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS:Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS:The levels of IL-33 and sST2,and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC.The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI),erythrocyte sedimentation rate (ESR),proteinuria and triglyceride,but negatively associated with complement C3.IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR).Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R2 =0.442),especially CKD staging.CONCLUSION:Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury.IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.%目的:探讨新型内源性警报素白细胞介素33(interleukin-33,IL-33)/致癌性抑制因子2(suppression of tumorigenicity 2,ST2)途径与系统性红斑狼疮(systemic lupus erythematosus,SLE)肾脏损害及疾病活动度的相关性.方法:ELISA检测50例SLE患者和30例健康对照者(healthy control,HC)血清的可溶性ST2(soluble ST2,sST2)和IL-33浓度.结果:SLE患者的血清sST2 、IL-33浓度及IL-33/sST2比值均显著高于HC.SLE患者的血清sST2浓度与红细胞沉降率(erythrocyte sedimentation rate,ESR)、SLE疾病活动度指数(SLE disease activity index,SLEDAI) 、24 h尿蛋白、甘油三酯呈正相关,与补体C3呈负相关,线性回归示SLEDAI及甘油三酯作为主要因素影响sST2水平升高(R2 =0.432).SLE患者血清IL-33浓度与SLEDAI、ESR 、24 h尿蛋白、慢性肾脏病(chronic kidney disease,CKD)分期、甘油三酯呈正相关,与C3、C4、估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)、白蛋白呈负相关,线性回归示SLEDAI、C3及eGFR作为主要因素影响IL-33水平升高(R2=0.380).SLE患者的血清IL-33/sST2比值与SLEDAI、eGFR呈正相关,与病程、起病年龄、激素用量、CKD分期、血肌酐、C3、C4、白蛋白呈负相关,回归分析提示IL-33/sST2比值与CKD分期及白蛋白水平相关(R2=0.442),尤以CKD的相关性较强,该比值随CKD分期的加重而降低,当CKD分期为3级以上时IL-33/sST2比值显著下降.结论:IL-33/ST2参与SLE发病,血清IL-33和sST2均能一定程度地反映病情,sST2较IL-33与疾病活动度关联性更强;IL-33和sST2不能直接反映SLE的肾脏受累,但与间接反映SLE肾损伤的24 h尿蛋白及其它危险因素有关;IL-33/sST2比值的降低提示SLE肾脏的慢性、中重度损害.