用于鉴别诊断活动性和潜伏性结核病候选宿主血浆免疫调节因子和抗体谱的分析鉴定  

Analysis and identification of plasma immunoregulatory factors and antibody profiles of candidate hosts for diagnosis of active and latent tuberculosis infection

作　　者：王婉如 张权武 卢琼 郭乐 WANG Wanru;ZHANG Quanwu;LU Qiong;GUO Le(Department of Tuberculosis,Shaanxi Provincial Institute of Tuberculosis Prevention and Treatment,Xi’an 710100,China)

机构地区：[1]陕西省结核病防治院结核内科,西安710100 [2]陕西省结核病防治院重症医学科,西安710100

出　　处：《传染病信息》2024年第6期520-526,共7页Infectious Disease Information

基　　金：陕西省重点研发计划项目(2020SF-105)。

摘　　要：目的探讨血浆免疫调节因子和抗体谱在活动性结核病(active tuberculosis,ATB)和潜伏性结核病(latent tuberculosis,LTBI)鉴别诊断中的应用价值。方法选择2023年1月至2023年12月陕西省结核病防治院收治的84例ATB患者作为ATB组,并按1∶1纳入84例LTBI患者作为LTBI组。通过基于微球的Luminex多重免疫分析技术检测所有受试者血浆中10种免疫调节因子[白细胞介素(interleukin,IL)-6、IL-16、IL-18、干扰素γ(interferon-γ,IFN-γ)、CXC趋化因子配体(chemokine ligand 1,CXCL)1、CXCL10、CXCL9、粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和血小板衍化生长因子-BB(platelet-derived growth factor-BB,PDGF-BB)]以及抗体谱[Rv3881c、Rv 0934-P38、Rv2031c、Rv1886c、Rv1860、Rv3874、Rv1926c、Rv3841]的表达。比较上述指标在ATB组与LTBI组之间的差异并分析其对鉴别诊断ATB与LTBI的价值。结果ATB组CXCL10、CXCL9、IL-18、IL-6、IL-16、PDGF-BB、IFN-γ、CXCL1、G-CSF、VEGF水平均显著高于LTBI组(P均<0.05)。ATB组抗体Rv3881c、Rv0934-P38、Rv2031c、Rv1886c、Rv1860、Rv3874、Rv1926、Rv3841表达也显著高于LTBI组(P均<0.05)。将血浆免疫调节因子和抗体谱纳入Lasso回归和Logistic回归模型,进一步筛选确定CXCL10、CXCL9、CXCL1、G-CSF、Rv3881c、Rv2031c、Rv1860是鉴别ATB和LTBI的显著预测因素(P均<0.05)。4种血浆免疫调节因子联合区分ATB和LTBI的受试者工作特征曲线下面积(area under curve,AUC)为0.888(95%CI:0.841~0.935),3种抗体联合区分ATB和LTBI的AUC为0.866(95%CI:0.807~0.925),均显著高于各标志物单独预测的AUC(P均<0.05)。4种免疫调节因子和3种抗体联合用于ATB和LTBI的鉴别诊断价值进一步提高,AUC可达到0.984(95%CI:0.969~0.998)。结论血浆免疫调节因子和抗体谱的联合检测可能是区分ATB和LTBI的有用方法。Objective This study aimed to evaluate the diagnostic value of plasma immunoregulatory factors and antibody profiles in differentiating active tuberculosis(ATB)from latent tuberculosis infection(LTBI).Methods A total of 84 ATB patients admitted to the hospital between January 2023 and December 2023 were included in the ATB group,while 84 LTBI patients were matched 1∶1 to form the LTBI group.Plasma levels of immunoregulatory factors,including interleukin(IL)-6,IL-16,IL-18,interferon-γ(IFN-γ),chemokine ligand 1(CXCL1),granulocyte colony-stimulating factor(G-CSF),CXCL10,CXCL9,vascular endothelial growth factor(VEGF),and platelet-derived growth factor-BB(PDGF-BB),along with antibodies targeting Rv3881c,Rv0944-P38,Rv2031c,Rv1886c,Rv1860,Rv3874,Rv1926c,and Rv3841,were measured using the Luminex multiplex immunoassay based on microspheres.Results Plasma levels of CXCL10,CXCL9,IL-18,IL-6,IL-16,PDGF-BB,IFN-γ,CXCL1,G-CSF,and VEGF were significantly elevated in the ATB group compared to the LTBI group(P<0.05).Similarly,the expression of anti-Mtb antibodies Rv3881c,Rv0944-P38,Rv2031c,Rv1886c,Rv1860,Rv3874,Rv1926c,and Rv3841 was significantly higher in the ATB group(P<0.05).Lasso and Logistic regression analyses identified CXCL10,CXCL9,CXCL1,G-CSF,Rv3881c,Rv2031c,and Rv1860 as significant predictors for distinguishing ATB from LTBI(P<0.05).The area under the ROC curve(AUC)for the combined plasma immunoregulatory factors in differentiating ATB from LTBI was 0.888(95%CI:0.841-0.935),and the AUC for the antibody profiles was 0.866(95%CI:0.807-0.925),both significantly higher than those of individual markers(P<0.05).The combined use of the four immunoregulatory factors and three antibody profiles further improved diagnostic accuracy,achieving an AUC of 0.984(95%CI:0.969-0.998).Conclusion The combined detection of plasma immunoregulatory factors and antibody profiles provides a highly effective method for differentiating ATB from LTBI,with potential clinical utility.

关 键 词：活动性结核病 潜伏性结核感染 免疫调节因子 抗体 

分 类 号：R52[医药卫生—内科学]