NLRP3炎性小体水平检测在非霍奇金淋巴瘤患者免疫治疗相关细胞因子风暴及化疗相关间质性肺炎中的预测价值分析  

Predictive value of NLRP3 inflammasome level detection in immunotherapy-related cytokine storm and chemotherapy-related interstitial pneumonia in patients with non-Hodgkin lymphoma

作　　者：张艳彬[1] 陈文昆[1] 周寅[1] 张小娟[1] 李魁星[1] Zhang Yanbin;Chen Wenkun;Zhou Yin;Zhang Xiaojuan;LI Kuixing(Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China)

机构地区：[1]北京协和医院血液内科,100730

出　　处：《疑难病杂志》2022年第5期485-491,506,共8页Chinese Journal of Difficult and Complicated Cases

基　　金：“中央高校基本科研业务费”项目(33332018013)。

摘　　要：目的分析NOD样受体家族3(NLRP3)炎性小体水平检测在非霍奇金淋巴瘤(NHL)患者免疫治疗相关细胞因子风暴(CRS)及化疗相关间质性肺炎(IP)中的预测价值。方法回顾性分析2019年3月—2021年4月在北京协和医院血液内科接受嵌合抗原受体T细胞(CAR-T)免疫治疗联合化疗的NHL患者125例临床资料,按照CAR-T免疫治疗期间是否出现CRS分为CRS组(n=99)、非CRS组(n=26),比较2组一般资料、基线外周血NLRP3炎性小体各基因mRNA表达、炎性细胞因子、血常规、血生化指标水平,经双变量Preason相关性分析NLRP3炎性小体表达与炎性细胞因子水平的相关性;根据化疗期间是否出现IP分为IP组(n=28)、非IP组(n=97),比较2组一般资料、基线外周血NLRP3炎性小体各基因mRNA表达及血常规、血生化指标水平;多因素Logistic回归分析影响NHL患者CRS、IP发生的危险因素;ROC曲线分析NLRP3炎性小体表达预测NHL患者CRS、IP发生的价值。结果CRS组外周血NLRP3、凋亡相关斑点样蛋白(ASC)、半胱氨酸蛋白酶-1(Caspase-1)的mRNA表达水平均高于非CRS组(t/P=9.546/<0.001、3.456/0.001、4.386/<0.001);CRS组外周血C反应蛋白(CRP)、白介素-6(IL-6)、IL-10、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、乳酸脱氢酶(LDH)水平均高于非CRS组(P<0.01);双变量Preason相关性显示,CRS患者外周血NLRP3、ASC、Caspase-1的mRNA表达均与CRP、IL-6、IL-10、IFN-γ、TNF-α、LDH水平呈正相关(P<0.01)。IP组外周血NLRP3、ASC、Caspase-1的mRNA表达水平均高于非IP组(t=27.931、4.890、6.319,P均<0.001);IP组血常规、血生化相关指标水平与非IP组相比,差异无统计学意义(P>0.05)。多因素Logistic回归分析显示,NLRP3、ASC、Caspase-1的mRNA表达升高均是影响NHL患者CRS、IP发生的危险因素(P<0.05);绘制ROC结果显示,NLRP3、ASC、Caspase-1及三者联合预测NHL患者CRS发生的AUC分别为0.890、0.715、0.800、0.916,预测IP发生的AUC分别为0.901、0.868、0Objective To analyze the predictive value of NOD-like receptor family 3(NLRP3)inflammasome level detection in immunotherapy-related cytokine storm(CRS)and chemotherapy-related interstitial pneumonia(IP)in patients with non-Hodgkin lymphoma(NHL).Methods The clinical data of 125 NHL patients who received chimeric antigen receptor T cell(CAR T)immunotherapy combined with chemotherapy in the Department of Hematology,Peking Union Medical College Hospital from March 2019 to April 2021 were retrospectively analyzed.CRS was divided into CRS group(n=99)and non-CRS group(n=26).The general data,baseline peripheral blood NLRP3 inflammasome gene mRNA expression,inflammatory cytokines,blood routine,and blood biochemical indexes were compared between the two groups,and the bivariate Pearson correlation was used to analyze the expression of NLRP3 inflammasome and inflammatory cytokines.horizontal correlation.According to whether IP occurred during chemotherapy,the patients were divided into IP group(n=28)and non-IP group(n=97).The general data,baseline peripheral blood NLRP3 inflammasome gene mRNA expression and blood routine and blood biochemical index levels were compared between the two groups.Multivariate Logistic regression analysis of risk factors for CRS and IP in NHL patients.The value of NLRP3 inflammasome expression in predicting the occurrence of CRS and IP in NHL patients was analyzed by ROC curve.Results The mRNA expression levels of NLRP3,apoptosis-associated speck-like protein(ASC),and cysteine protease 1(Caspase-1)in peripheral blood in the CRS group were higher than those in the non-CRS group(t/P=9.546/<0.001,3.456/0.001,4.386/<0.001).The levels of peripheral blood C-reactive protein(CRP),interleukin 6(IL-6),IL-10,interferonγ(IFN-γ),tumor necrosis factorα(TNF-α),and lactate dehydrogenase(LDH)in the CRS group were higher than those in the non-CRS group(P<0.01).Bivariate Pearson correlation showed that the mRNA expressions of NLRP3,ASC and Caspase-1 in peripheral blood of CRS patients were positively correlate

关 键 词：非霍奇金淋巴瘤 NOD样受体家族3炎性小体 细胞因子风暴 间质性肺炎 预测价值 

分 类 号：R563.13[医药卫生—呼吸系统] R733.7[医药卫生—内科学]