摘要
目的 探讨病原检测阴性且IGRA阴性患者外周血中CRP以及细胞因子表达水平的变化及其临床意义。方法 纳入2021年10月21日至2023年4月27日期间在苏州大学附属传染病医院住院病例295例。依据肺结核诊断标准（WS288~2017）纳入196例结核病患者，其中男性130例，女性66例，平均年龄58.4±17.1（岁）；菌阳性肺结核患者92例，菌阴性肺结核患者104例；在菌阴性肺结核（病原检测阴性）患者中，IGRA阳性患者44例，IGRA阴性患者14例。疾病对照组纳入肺炎患者79例，其中男性51例，女性28例，平均年龄61.8±15.4（岁）。健康对照组20例，其中男性10例，女性10例，平均年龄58.6±6.3（岁）。分别采用流式细胞术和免疫荧光干式定量法检测外周血中细胞因子（IFN-γ、IFN-α、IL-2、IL-4、IL-5、IL-6、IL-8、TNF-α、IL-10、IL-12P70、IL-1β、IL-17）及CRP的表达，分析不同组炎症细胞因子及CRP的表达差异。结果 ①菌阳性肺结核患者外周血IFN-γ、CRP、IL-6水平均显著高于菌阴性肺结核患者，且菌阴性肺结核患者外周血IFN-γ、CRP、IL-6水平均显著高于健康对照组，P分别为＜0.0001、0.0006、＜0.0001。②菌阴性肺结核患者中IGRA阴性患者外周血IFN-γ、CRP、IL-6水平均显著高于健康对照组，P分别为0.0002、0.0043、＜0.0001。③以健康对照组为参照，菌阴性肺结核患者中IGRA阴性患者的IFN-γ联合CRP 、IL-6 的ROC曲线下AUC为0.957，其敏感度、特异度分别为92.9%、100% 。④以疾病对照组为参照，菌阴性肺结核患者中IGRA阴性患者的IFN-γ联合CRP 、IL-6 的ROC曲线下AUC为0.736，敏感度、特异度分别为50%、89.9%。结论 临床有肺结核疑似症状且影像学高度支持的患者，在无病原学诊断依据且IGRA阴性时，外周血IFN-γ联合CRP、IL-6检测可为该类疑似结核病患者提供辅助诊断。
关键词： 菌阴性肺结核；IGRA阴性；IFN-γ；CRP；IL-6
Abstract
Objective To investigate the changes in CRP and cytokine expression levels in the peripheral blood of patients with negative pathogen tests and negative IGRA and their clinical significance. Methods Two hundred and ninety-five cases hospitalized in the Infectious Diseases Hospital affiliated with Soochow University between October 21, 2021 and April 27, 2023 were included. Based on the diagnostic criteria for tuberculosis (WS288~2017), 196 cases of tuberculosis patients were included, including 130 males and 66 females, with a mean age of 58.4±17.1 (years); 92 cases of bacteriophage-positive tuberculosis patients and 104 cases of bacteriophage-negative tuberculosis patients; among the bacteriophage-negative tuberculosis (pathogen test-negative) patients, there were 44 cases of IGRA-positive patients and IGRA-negative patients 14 cases. The disease control group included 79 patients with pneumonia, including 51 males and 28 females, with a mean age of 61.8±15.4 (years). The healthy control group included 20 cases, of which 10 were male and 10 were female, with a mean age of 58.6±6.3 (years). The expression of cytokines (IFN-γ, IFN-α, IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, IL-10, IL-12P70, IL-1β, IL-17) and CRP in the peripheral blood were detected by flow cytometry and immunofluorescence dry-quantification, respectively, and the expression differences of inflammatory cytokines and CRP in different groups were analyzed. Results ①Peripheral blood levels of IFN-γ, CRP, and IL-6 were significantly higher in bacteria-positive TB patients than in bacteria-negative TB patients, and peripheral blood levels of IFN-γ, CRP, and IL-6 were significantly higher in bacteria-negative TB patients than in healthy controls, with P <0.0001, 0.0006, and <0.0001, respectively. ②Peripheral blood levels of IFN-γ, CRP, and IL-6 were significantly higher in IGRA-negative patients with mycobacterium-negative tuberculosis than in healthy controls, with P of 0.0002, 0.0043, and <0.0001, respectively. ③Using the healthy control group as a reference, the AUC under the ROC curve of IFN-γ combined with CRP and IL-6 in bacteria-negative tuberculosis patients with IGRA-negative patients was 0.957, and its sensitivity and specificity were 92.9% and 100%, respectively. ④Using the disease control group as a reference, the AUC under the ROC curve for IFN-γ combined with CRP , IL-6 in bacteriophage-negative TB patients with IGRA-negative patients was 0.736, and the sensitivity and specificity were 50% and 89.9%, respectively. Conclusion s In patients with clinically suspected symptoms of tuberculosis and highly supportive imaging, peripheral blood IFN-γ combined with CRP and IL-6 testing may provide an adjunctive diagnosis for this group of patients with suspected tuberculosis when there is no basis for an aetiologic diagnosis and IGRA is negative.
Key words： Tuberculosis; Professional pneumoconiosis; IFN-γ; CRP; IL-6
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