基于NF-κB/NLRP3/Caspase-1信号通路的类风湿关节炎合并感染的致病机制

Pathogenesis mechanisms of NF-κB/NLRP3/Caspase-1 signaling pathways in rheumatoid arthritis patients complicated with infection

目的探究核因子-κB(NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)/胱氨酸蛋白酶-1(Caspase-1)信号通路在类风湿关节炎(RA)合并感染致病中的机制。方法选取天津市第一中心医院2021年6月-2023年6收治的RA合并感染患者80例为感染组,RA未合并感染患者80例为未感染组,同期体检的健康人群80名为对照组,分析RA合并感染的类型分布,检测三组受试者外周血NF-κB、NLRP3、caspase-1、白细胞介素(IL)-1β及IL-18水平,受试者工作特征(ROC)曲线分析NF-κB、NLRP3、Caspase-1对RA合并感染的诊断价值。结果80例RA合并医院感染患者感染类型主要为尿路感染和皮肤感染,分别占37.50%和36.25%;感染组NF-κB、NLRP3、Caspase-1、IL-1β及IL-18水平均高于未感染组和对照组(P<0.05),且未感染组高于对照组(P<0.05);ROC曲线分析结果显示,NF-κB、NLRP3和Caspase-1对RA合并感染的诊断效能较高(P<0.05),曲线下面积(AUC)分别为0.934、0.817和0.821。结论NLRP3/Caspase-1信号通路的异常激活会促进炎症因子IL-1β及IL-18的释放,加剧免疫炎症反应,可作为RA合并感染的潜在诊断标志物。

OBJECTIVE To explore the pathogenic mechanisms of nuclear factor-κB(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathways in the infection of the patients with rheumatoid arthritis(RA).METHODS A total of 80 RA patients who were complicated with infection and treated in Tianjin First Central Hospital from Jun 2021 to Jun 2023 were assigned as the infection group,and 80 RA patients who were not complicated with infection were assigned as the no infection group.Meanwhile,80 healthy people who received physical examination were chosen as the control group.The types of the infection were analyzed,the levels of peripheral blood NF-κB,NLRP3,caspase-1,interleukin(IL)-1βand IL-18 were detected for the three groups of participants.The values of NF-Κb,NLRP3 and Caspase-1 in diagnosis of the infection were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Urinary tract infection and skin infection were the major types of nosocomial infection among the 80 RA patients,accounting for 37.50%and 36.25%,respectively.The levels of NF-κB,NLRP3,Caspase-1,IL-1βand IL-18 of the infection group were higher than those of the no infection group and the control group(P<0.05),and the levels of the above indexes of the no infection group were significantly higher than those of the control group(P<0.05).The ROC curve analysis showed that NF-κB,NLRP3 and Caspase-1 had high diagnostic efficiencies for infection in the RA patients,and the areas under curves(AUCs)were 0.934,0.817 and 0.821,respectively.CONCLUSION The abnormal activation of NLRP3/Caspase-1 signaling pathways may promote the release of inflammatory factors IL-1βand IL-18 and aggravate the immune-inflammatory response.The indexes can serve as potential diagnostic markers for the infection in the RA patients.