耐多药结核病患者细胞免疫功能的初步研究

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,MDR-TB)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(healthycontrol,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。

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

Objective To dynamically observe the cellular immune function of the patients with multidrug-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-γ, 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-10 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 multidrug-resistant tuberculosis is further exacerbated and presents more significant indicator changes. Their disease conditions are more complex and increase the difficulty of clinical treatment.