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复治涂阳肺结核患者细胞因子和可溶性黏附分子谱及生物标志物用于治疗监测。

Cytokine and soluble adhesion molecule profiles and biomarkers for treatment monitoring in Re-treated smear-positive patients with pulmonary tuberculosis.

机构信息

Army Tuberculosis Prevention and Control Key Laboratory, Beijng Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, PR China.

Army Tuberculosis Prevention and Control Key Laboratory, Beijng Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, PR China.

出版信息

Cytokine. 2018 Aug;108:9-16. doi: 10.1016/j.cyto.2018.03.009. Epub 2018 Mar 16.

DOI:10.1016/j.cyto.2018.03.009
PMID:29554572
Abstract

Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment. Levels of 18 serum cytokines and soluble adhesion molecules were measured by a high-throughput Cytometric Bead Array. At baseline, IL-1, IL-2, IL-12P70, and soluble CD62E levels were significantly higher in PTB patients than those in the healthy controls (p < 0.05); IL-4, IL-5, IL-7, IL-8, IL-10, IL-17, IL-21, soluble CD54, MIG, and TGF-β levels in PTB patients were significantly lower than those in the healthy controls (p < 0.05), of which TGF-β, IL-7, IL-8, IL-10, soluble CD54, and MIG were most notably (p < 0.0005). After re-treatment, IFN-γ, IL-2, IL-7, and soluble CD54 levels and IL-2/IL-10 and IFN-γ/IL-10 ratios showed an upward trend during the re-treatment period. They were more sensitive than other cytokines and adhesion molecules and could be effective as serum indicators for re-treatment response. The immune response was imbalance in treated smear-positive PTB patients: Th1 response was elevated, but Th2 and Th17 responses were reduced. Systematic and comprehensive understanding of the cytokine and soluble adhesion molecule profiles provides a theoretical basis for immuno-diagnosis, immunotherapy, and immuno-monitoring of Re-treated PTB patients.

摘要

肺结核(PTB)的复发与宿主免疫系统未能控制入侵的结核分枝杆菌有关。严重的免疫缺陷或免疫紊乱可能是 TB 复发的主要原因。本研究旨在定量检测复治涂阳肺结核(PTB)患者在重新接受抗结核药物治疗前后血清中炎症细胞因子和可溶性黏附分子的水平。研究共纳入了 30 名健康对照者和 215 名活动性初治 PTB 患者,在基线、治疗后 2、4、6 个月时采集血清样本,采用高通量流式微球阵列技术检测 18 种细胞因子和可溶性黏附分子的水平。与健康对照组相比,PTB 患者在基线时的白细胞介素(IL)-1、IL-2、IL-12P70 和可溶性细胞间黏附分子-1(sICAM-1)水平显著升高(p<0.05),IL-4、IL-5、IL-7、IL-8、IL-10、IL-17、IL-21、可溶性细胞间黏附分子-1(sICAM-1)、单核细胞趋化蛋白-1(MIG)和转化生长因子-β(TGF-β)水平显著降低(p<0.05),其中 TGF-β、IL-7、IL-8、IL-10、sICAM-1 和 MIG 降低最显著(p<0.0005)。在重新治疗后,IFN-γ、IL-2、IL-7 和 sICAM-1 水平以及 IL-2/IL-10 和 IFN-γ/IL-10 比值在重新治疗期间呈上升趋势。它们比其他细胞因子和黏附分子更敏感,可作为重新治疗反应的有效血清指标。在复治涂阳 PTB 患者中,免疫反应失衡:Th1 反应升高,但 Th2 和 Th17 反应降低。系统全面地了解细胞因子和可溶性黏附分子谱为复治 PTB 患者的免疫诊断、免疫治疗和免疫监测提供了理论依据。

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