过敏性紫癫患儿外周血单个核细胞中ASC mRNA和NLRP3 mRNA表达水平及其与并发肾炎的关系

Expression levels of ASC mRNA and NLRP3 mRNA in peripheral blood monocytes of children with HSP and their relationships with complication of HSP nephritis

摘要

目的 探讨过敏性紫癫(HSP)患儿外周血单个核细胞中炎性体凋亡相关斑点样蛋白(ASC)mRNA和核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)mRNA表达水平及其与并发肾炎的关系。方法 选择2020年7月至2022年12月于菏泽市立医院就诊的76例HSP患儿为观察组,收集其临床资料;以同期在院体检的48例健康儿童为对照组.根据患儿是否并发肾炎,将观察组分为过敏性紫癜肾炎(HSPN)组22例与HSP组54例.比较观察组与对照组、HSPN组和HSP组及对照组的临床资料,采用Logistic回归模型分析HSP患儿并发肾炎的危险因素,采用限制性立方样条模型分析ASC mRNA和NLRP3 mRNA与HSP患儿并发肾炎的关系.利用y=1-1/(1+e^-z)回归方程建立HSP患儿并发肾炎的预测模型,以十字交叉验证法验证模型的稳定性。结果 观察组与对照组的体质量指数(BMI)、白细胞(WBC)、血小板(PLT)、红细胞(RBC)、中性粒细胞(NEU)、C反应蛋白(CRP)、甘油三酯(TG)、血清肌酐(Scr)、尿素氮(BUN)、尿微量白蛋白(mALB)、纤维蛋白原(FIB)、纤维蛋白原降解产物(FDP)、D-二聚体(D-D)、低密度脂蛋白胆固醇(LDL-C)、免疫球蛋白(Ig)A、IgG、IgM、白细胞介素(IL)-16、IL-18、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)、胱抑素(CysC)、肿瘤标志物(TM)、血管性血友病因子(vWF)、血管细胞间黏附分子-Ⅰ(sVCAM-Ⅰ)、结缔组织生长因子(CTGF)、基质金属蛋白酶9(MMP9)、ASC mRNA、NLRP3 mRNA比较,差异均有统计学意义(t=2.587~22.473,P<0.05).调整相关混杂因素后,按照总HSP切点将ASC mRNA转化为二分类变量后,与低ASC mRNA表达水平比较,高ASC mRNA表达水平与HSP有关联(OR=0.723,95%CI:0.672~0.831,P<0.001);按照总HSP切点将NLRP3 mRNA转化为二分类变量后,与低NLRP3 mRNA表达水平比较,高NLRP3 mRNA表达水平与HSP有关联(OR=0.642,95%CI:0.611~0.791,P<0.001).HSPN组、HSP组和对照组的BMI、WBC、PLT、RBC、NEU、CRP、TG、Scr、BUN、mALB、FIB、FDP、D-D、IgA、IgG、IgM、IL-16、IL-18、IGF-1、IGFBP-3、CysC、TM、vWF、sVCAM-Ⅰ、CTGF、MMP9、ASC mRNA、NLRP3 mRNA比较,差异均有统计学意义(t=2.461~27.327,P<0.05).多因素Logistic回归模型分析显示,Scr≥92.16μmol/L、BUN≥7.74mmol/L、mALB≥0.58mg/L、D-D≥1.12mg/L、IgA≥2.54g/L、IGF-1≥0.77ng/L、IGFBP-3≥0.74ng/L、CysC≥2.23ng/L、sVCAM-Ⅰ≥111.37ng/L、MMP9≥23.71ng/L、ASC mRNA≥22.55和NLRP3 mRNA≥21.98均是HSP患儿并发肾炎的危险因素(P<0.05).限制性立方样条模型分析ASC mRNA和NLRP3 mRNA与HSP患儿并发肾炎的关系显示,ASC mRNA、NLRP3 mRNA均与HSP患儿并发肾炎存在非线性的剂量-反应关系.以HSP患儿并发肾炎的危险因素建立预测模型,并对其稳定性进行验证,模型具有良好的预测精准度。结论 HSP患儿外周血单个核细胞中ASC mRNA、NLRP3 mRNA表达水平与患儿并发肾炎均存在关联.临床上应加强对ASC和NLRP3的监测,以减少HSP患儿并发肾炎的发生.

Abstract

Objective To investigate expression levels of inflammasome apoptosis-associated speck-like caspases (ASC) mRNA and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) mRNA in peripheral blood monocytes of children with allergic purpura [Henöch-Schönlein purpura (HSP)] and their relationships with HSP complicated nephritis (HSPN). Methods 76 children with HSP who were treated in Heze Municipal Hospital from July 2020 to December 2022 were included in observation group. 48 healthy children who underwent physical examination in the hospital during the same period were selected as control group. According to whether the child had HSP complicated nephritis, the children in the observation group were divided into HSPN group (n=22) and HSP group (n=54). The clinical data of the children in HSPN group, HSP group and the control group were collected, analyzed and compared. Logistic regression model was used to analyze risk factors of complication of HSPN in the children with HSP. Restricted cubic spline (RCS) model was used to analyze correlations of ASC mRNA and NLRP3 mRNA with HSPN. The prediction model of HSPN was established by using y=1-1/(1+e^-z) regression equation, and stability of the model was verified by cross-validation method. Results There were significant differences in body mass index (BMI), white blood cell count (WBC), platelet count (PLT), red blood cell count (RBC), neutrophilic granulocyte count (NEU), C-reactive protein (CRP), triglyceride (TG), serum creatinine (Scr), blood urea nitrogen (BUN), micro-albumin (mALB), fibrinogen (FIB), fibrinogen degradation products (FDP), D-dimer (D-D), low density lipoprotein cholesterol (LDL-C), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-16 (IL-16), interleukin-18 (IL-18), insulin-like growth factors-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cystatin C (CysC), tumor marker (TM), von Willebrand factor (vWF), vascular intercellular adhesion molecule-Ⅰ (sVCAM-Ⅰ), connective tissue growth factor (CTGF), metalloproteinase 9 (MMP9), ASC mRNA and NLRP3 mRNA of the children between the observation group and the control group (t=2.587-22.473, all P<0.05). After adjusting for relevant confounders, and after ASC mRNA was converted into binary variables according to the total HSP cut-off point, higher ASC mRNA level was associated with HSP as compared with lower ASC mRNA level (OR=0.723, 95%CI: 0.672-0.831, P<0.001). After converting NLRP3 mRNA into a binary variable according to the total HSP cut-off point, higher NLRP3 mRNA level was associated with HSP as compared with lower NLRP3 mRNA level (OR=0.642, 95%CI: 0.611-0.791, P<0.001). In BMI, WBC, PLT, RBC, NEU, CRP, TG, Scr, BUN, mALB, FIB, FDP, D-D, IgA, IgG, IgM, IL-16, IL-18, IGF-1, IGFBP-3, CysC, TM, vWF, sVCAM-I, CTGF, MMP9, ASC mRNA and NLRP3 mRNA, there were statistically significant differences among HSPN group, HSP group and the control group (t=2.461-27.327, all P<0.05). Multivariate Logistic regression model analysis showed that Scr≥92.16μmol/L, BUN≥7.74mmol/L, mALB≥0.58mg/L, D-D≥1.12mg/L, IgA≥2.54g/L, IGF-1≥0.77ng/L, IGFBP-3≥0.74ng/L, CysC≥2.23ng/L, sVCAM-I≥111.37ng/L, MMP9≥23.71ng/L, ASC mRNA≥22.55 and NLRP3 mRNA≥21.98 were all risk factors for HSP complicated with nephritis in children (all P<0.05). The RCS model analysis results showed that there were nonlinear dose-response relationships of ASC mRNA and NLRP3 mRNA with HSPN in the children with HSP (both P<0.001). The prediction model of HSP complicated with nephritis (HSPN) based on the risk factors was verified and showed that it had a good stability and a good prediction accuracy. Conclusion The expression levels of ASC mRNA and NLRP3 mRNA in peripheral blood monocytes of HSP children are associated with HSPN. Clinical monitoring for ASC and NLRP3 should be strengthened to reduce incidence of HSPN in children with HSP.

关键词

过敏性紫癫 / 过敏性紫癜肾炎 / 凋亡相关斑点样蛋白 / 核苷酸结合寡聚化结构域样受体蛋白3 / 患儿

Key words

Henöch-Schönlein purpura / Henöch-Schönlein purpura nephritis / apoptosis-associated speck-like caspase / nucleotide-binding oligomerization domain-like receptor protein 3 / children

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基金资助

山东省高等学校科技计划项目(J17KB084)