Analysis of Plasma Cytokine and Chemokine Profiles in Patients with and without Tuberculosis by Liquid Array-Based Multiplexed Immunoassays.

Analysis of Plasma Cytokine and Chemokine Profiles in Patients with and without Tuberculosis by Liquid Array-Based Multiplexed Immunoassays.
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通过基于液体阵列的多重免疫分析分析结核病患者和非结核病患者的血浆细胞因子和趋化因子谱

DOI:
10.1371/journal.pone.0148885
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Ma L
Ma L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xiong W;Dong H;Wang J;Zou X;Wen Q;Luo W;Liu S;He J;Cai S;Ma L

文献摘要

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本研究的目的是建立3种不同表现的活动性结核病(TB)患者的血浆细胞因子/趋化因子谱,并与接种卡介苗(BCG)的健康个体和其他肺部疾病患者(非结核病患者)的谱进行比较。为此,收集了151例结核病患者的血浆样本,其中包括68例肺结核(PTB)、43例支气管内结核(支气管内结核)和40例结核性胸膜炎(TP)患者,以及107例非结核病患者(包括26例非结核病患者)和81例接种过bcg的健康对照。基于液体阵列的多路免疫分析法用于筛选血浆样品中20种不同的细胞因子和趋化因子。使用多项逻辑回归分析细胞因子/趋化因子与TB/非TB患者之间的关系。与非结核病供者相比,结核病患者血浆中促炎细胞因子/趋化因子TNF-α、IL-6、IP-10、IFN-γ和MIP-1β的中位水平显著升高,这表明它们可能作为诊断结核病的生物标志物。与健康供体的进一步比较表明,在所有3种类型的结核病患者的血浆中,只有中位TNF-α血浆水平高。血浆IL-6含量仅在TP患者中升高,而血浆IP-10、IFN-γ和MIP-1β水平在PTB和TP患者中均显著升高。出乎意料的是,在上述细胞因子/趋化因子中,与健康供者相比,MIP-1β在非结核病患者中也高表达。我们的研究结果表明,TNF-α可能是诊断三种结核表现形式的理想生物标志物,而其他因子(IL-6、IP-10、MCP-1和IFN-γ)可能有助于三种结核表现类型的鉴别诊断。进一步表征与不同类型结核病相关的免疫反应将为开发新的结核病诊断方法提供基础。
The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1β were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1β were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1β was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics.