耐多药结核病患者细胞免疫功能的初步研究

Preliminary study on cellular immune function of patients with multidrug-resistant tuberculosis

目的动态观察耐多药结核病患者机体细胞免疫状态,为临床诊治用药提供支持,为以后耐多药结核病的免疫治疗打下初步基础。方法用绝对浓度法进行药敏试验,筛选出耐多药结核(Multi-drug resistant tuberculosis,MDRTB)患者50例,药物敏感性结核(drug-susceptible tuberculosis,S-TB)患者50例,另于体检者中选取健康对照(healthy control,HC)20例,流式细胞分析淋巴细胞亚群(CD4^+、CD3^+、CD8^+分子等),酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清细胞因子(IFN-γ、IL-2、IL-4和IL-10等),比较耐多药结核病患者血清学与全敏结核病患者血清、正常人血清之间的差异。结果各组间CD3^+分子百分比差异无统计学意义,健康组与各结核组CD4+、CD8^+、CD4^+/CD8^+百分比差异有统计学意义,耐多药结核组与结核敏感组CD4^+、CD8^+、CD4^+/CD8^+百分比差异有统计学意义。健康组与各结核组IFN-γ、IL-2、IL-4和IL-10的浓度差异均有统计学意义,耐多药结核组与结核敏感组IL-2、IL-4和IL-10的浓度差异有统计学意义。耐多药结核组CD4^+、CD4^+/CD8^+比值、IL-2显著低于结核敏感组,CD8^+、IL-4和IL-10显著高于结核敏感组(P<0.05)。结论结核病患者细胞免疫功能均下降,表现为CD4^+淋巴细胞百分比降低,CD8^+淋巴细胞百分比升高,CD4^+/CD8^+比值降低甚至倒置,增强抗结核免疫反应的细胞因子IFN-γ、IL-2浓度降低而抑制此反应的细胞因子IL-4和IL-10浓度升高。耐多药结核病患者较敏感结核病患者的细胞免疫功能进一步下降,表现为上述变化更加显著,使病情表现更加复杂及增加了治疗难度。

Objective To dynamically observe the cellular immune function of the patients with muhidrug-resistant tuberculosis （ MDR-TB ） so as to provide supports for clinical diagnosis, treatment and rational drug use and to lay a preliminary foundation for immunotherapy for MDR-TB patients. Methods Drug sensitivity test were performed on 50 MDR-TB patients and 50 drug -susceptible TB （ S-TB ） patients by the absolute concentration method. 20 healthy controls were selected from the physical examination centre. Lymphocyte subsets （ CD4＋ , CD3 ＋and CD8＋, etc. ） were analyzed by flow cytometry. Serum cytokines （ IFN-γ, IL -2, IL-4 and IL-10, etc. ） were detected by enzyme-linked immunosorbent assay （ ELISA）. Serological differences were compared among the MDR-TB patients, S-TB patients and healthy controls. Results No statistically significant difference was found in the percentage of CD3＋ among the three groups. There were significant differences in the percentages of CD4＋ , CD8＋ and CD4＋/CD8＋ between any two groups among the MDR-TB group, S-TB group and control group. There were also significant differences in the serum concentrations of IFN-7, IL-2, IL-4 and IL-10 between the control group and MDR-TB group or S-TB group as well as in the serum concentrations of IL-2, IL-4 and IL-IO between the MDR-TB group and S-TB group. The serum levels of CD4＋ , IL-2, and CD4＋/CD8＋ ratio in the MDR-TB group were all significantly lower than those of the S-TB group, while CD8＋, IL-4 and IL- 10 in the MDR-TB group were all significantly higher than those of S-TB group （P〈0.05）. Conclusions The cellular immune function of tuberculosis patients is impaired, which manifests as declined percentage of CD4＋ lymphocyte, elevated percentage of CD8＋ lymphocyte, reduced or even inverted ratio of CD4＋/CD8＋. As compared with patients with drug-susceptible tuberculosis, the cellular immune function of the patients with muhidrug-resistant tuberculosis is further exacerbated and presents more significant indicator changes. Their disease conditions are more complex and increase the difficulty of clinical treat- ment.