γ干扰素诱导蛋白-10和细胞因子在结核不同感染状态患者中的表达及意义

Expression and significance of interferon-inducible protein-10 and cytokines in patients with different infection status of tuberculosis

目的 本研究旨在观察外周血γ干扰素诱导蛋白-10(interferon γ-inducible protein-10, IP-10)与多种细胞因子在结核不同感染状态患者中的表达水平及其临床意义,并评估潜伏性结核感染(latent tuberculosis infection, LTBI)在向活动性结核病(active tuberculosis, ATB)发展过程中的效能。方法 收集分析昆明市第三人民医院2023年3月—2024年2月门诊与住院患者76例,分为ATB组(31例,男性17例,年龄中位数33岁)、LTBI组(27例,男性17例,年龄中位数29岁)和健康体检者(healthy control, HC)组(18例,男性11例,年龄中位数25岁)。采取3组的外周血样本,采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)分别检测IP-10、细胞因子白细胞介素6(interleukin, IL-6)、IL-4、IL-8、IL-10、IL-12、IL-2和肿瘤坏死因子α(tumor necrosis factor, TNF-α)的表达水平。数据类型为正态分布样本采用t检验,偏态分布采用Mann-Whitney U秩和检验;多组间比较首先采用Kruskal-Wallis H检验,然后采用Dunn's多重检验进行多组间两两比较,最后分析各细胞因子在区分不同人群组别时的效能。结果 外周血IP-10在LTBI、ATB组表达水平高于HC组,但受试者操作特征(receiver operating characteristic, ROC)曲线下面积(area under curve, AUC)显示灵敏度中等(AUC:0.7~0.9),特异度低(AUC:0.5~0.7)。IL-6表达水平由高到低依次为ATB组、LTBI组、HC组,其中HC组显著低于ATB组与LTBI组(F=12.15,P<0.001)。AUC结果显示ATB组的灵敏度与特异度均高于HC组。结论 IP-10在区分不同结核病状态方面表现出优势,单一细胞因子的预测效能有限,联合使用IL-6等多种细胞因子,结合临床表现,以期建立更为准确和全面的预测模型。

Objective The aim of this study was to observe the expression levels and clinical significance of peripheral blood interferonγ-inducible protein-10(IP-10)and various cytokines in patients with different infection statuses of tuberculosis and to assess the efficacy of latent tuberculosis infection(LTBI)in the progression to active tuberculosis(ATB).Methods Seventy-six outpatient and inpatient cases from the Third People's Hospital of Kunming were collected and analyzed from March 2023 to February 2024.The patients were divided into three groups:ATB group(31 cases,17 males,median age 33 years),LTBI group(27 cases,17 males,median age 29 years),and healthy control(HC)group(18 cases,11 males,median age 25 years).Peripheral blood samples from the three groups were taken and the expression levels of IP-10 and cytokines IL-6,IL-4,IL-8,IL-10,IL-12,IL-2,and TNF-αwere detected using enzyme-linked immunosorbent assay(ELISA)methods.The t-test was used for normally distributed samples,while the Mann-Whitney U test was used for skewed distributions.For comparisons between multiple groups,the Kruskal-Wallis H test was first employed,followed by Dunn's multiple comparison test for pairwise comparisons.Finally,the effectiveness of each cytokine in distinguishing different population groups was analyzed.Results The expression levels of peripheral blood IP-10 were higher in the LTBI and ATB groups than in the HC group,but the area under the curve(AUC)of the receiver operating characteristic(ROC)of the subjects showed moderate sensitivity(AUC:0.7-0.9)and low specificity(AUC:0.5-0.7).The IL-6 expression levels were in the order of high to low in the ATB group,LTBI group,and HC group,where the HC group was significantly lower than the ATB and LTBI groups(F=12.15,P<0.001).The sensitivity and specificity of the ATB group were higher than those in the HC group.Conclusions IP-10 exhibits unique advantages in distinguishing different tuberculosis statuses.The predictive efficacy of a single cytokine is limited.Combining multiple cytokines such as IL-6 with clinical manifestations,a more accurate and comprehensive prediction model can be established.