血清RAGE、HMGB1水平与重症肺炎急性呼吸窘迫综合征发病及IFN-γ/IL-4变化的关系

Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN⁃γ/IL⁃4 ratio in patients with severe pneumonia

目的探究血清晚期糖基化终产物受体(RAGE)、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)水平与重症肺炎(SP)急性呼吸窘迫综合征(ARDS)发病及γ-干扰素(IFN-γ)/白细胞介素4(IL-4)变化的关系。方法前瞻性选取2020年3月至2022年2月我院收治的100例SP患儿为研究对象,根据患儿是否发生继发性ARDS将患儿分为ARDS组(n=56)和对照组(n=44),收集患儿一般资料,采集外周血以酶联免疫吸附法进行RAGE、HMGB1、IFN-γ和IL-4表达水平检测,采用多因素logistic回归分析SP患儿继发ARDS的影响因素,采用Pearson相关性分析其与IFN-γ/IL-4的相关性,并采用受试者工作曲线(ROC)分析RAGE、HMGB1表达对SP患儿继发ARDS的预测价值。结果两组SP患儿性别、年龄、体温以及发病季节之间无显著差异,ARDS组致病菌种类多于对照组,PaO_(2)/FiO_(2)和APS评分、血清RAGE、HMGB1、IFN-γ和IL-4表达水平以及IFN-γ/IL-4比值均高于对照组(P<0.05)。经多因素logistic回归分析可知,致病菌种类、PaO_(2)/FiO_(2)、RAGE、HMGB1表达、IFN-γ、IL-4和IFN-γ/IL-4均为SP患儿继发ARDS的影响因素。经Pearson相关检验,SP患儿血清RAGE、HMGB1表达水平与IFN-γ、IL-4和IFN-γ/IL-4均呈正相关(P<0.05)。经ROC曲线分析可得,血清RAGE、HMGB1水平预测SP患儿发生ARDS的AUC分别为0.707和0.750,灵敏度分别为73.2%、64.3%,特异度分别为68.2%、77.3%,两者联合预测的AUC为0.848,灵敏度和特异度分别为80.4%和81.8%。结论SP继发ARDS患儿血清中RAGE、HMGB1表达水平较高,与IFN-γ/IL-4呈正相关,监测患儿血清RAGE、HMGB1表达对SP患儿继发ARDS的风险有一定的预测价值。

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End⁃Product(RAGE)and High⁃Mobility Group Protein B1(HMGB1)expression with the occurrence of acute respiratory distress syndrome(ARDS)and interferon⁃γ/interleukin⁃4(IFN⁃γ/IL⁃4)ratio in patients with severe pneumonia(SP).Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022,and the participants were classified into ARDS group(n=56)and control group(n=44)based on the occurrence of secondary ARDS.General informations werec⁃ollected.The expression of RAGE,HMGB1,IFN⁃γand IL⁃4 in peripheral blood was measured using Enzyme⁃Linked Immunosorbent Assay(ELISA).Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children,and the correlation with IFN⁃γ/IL⁃4 ratio was verified by pearson correla⁃tion analysis,moreover,receiver operating characteristic(ROC)curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children.Results There were no statistical difference in gender,age,body temperature and onset season between the two SP groups.The ARDS group had more types of pathogenic bacteria,larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction(PaO_(2)/FiO_(2)),higher Acute Physiological Score(APS),and up⁃regulated expression of RAGE,HMGB1,IFN⁃γand IL⁃4,as well as larger IFN⁃γ/IL⁃4 ratio than those of control group,with statistical difference(all P<0.05).Multivariate Logistic regression analysis revealed that pathogen type,PaO_(2)/FiO_(2) ratio,RAGE,HMGB1,IFN⁃γ,IL⁃4 and IFN⁃γ/IL⁃4 were the influencing factors for the occurrence of ARDS in children with SP.Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN⁃γ,IL⁃4 and IFN⁃γ/IL⁃4 ratio(P<0.05).ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750,with a sensitivity of 73.2%and 64.3%,and a specificity of 68.2%and 77.3%.The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848,providing a sensitivity and specificity of 80.4%and 81.8%respectively.Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS,and the two are positively correlated with IFN⁃γ/IL⁃4 ratio.Therefore,monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.