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

PLoS One. 2016 Feb 16;11(2):e0148885. doi: 10.1371/journal.pone.0148885. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BCG Vaccine / therapeutic use
  • Chemokine CCL2 / blood*
  • Chemokine CXCL10 / blood*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunoassay
  • Interferon-gamma / blood*
  • Interleukin-6 / blood*
  • Male
  • Mycobacterium tuberculosis / pathogenicity
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / classification
  • Tuberculosis, Pulmonary / pathology
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • BCG Vaccine
  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma

Grants and funding

This work was supported by National Science and Technology Key Projects on Major Infectious Diseases (2012ZX10003002-007) http://www.most.gov.cn/index.htm; National Natural Science Foundation of China (81371764, 81171539, 81571951) http://www.nsfc.gov.cn/; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2012) http://www.gdhed.edu.cn/; Guangdong Natural Science Foundation (2014A030313322) http://www.gdstc.gov.cn/; Science and Technology Project of Guangdong Province (2013B010404020) http://www.gdstc.gov.cn/; Scientific and Technological Innovation Project of Guangdong Province Discipline Construction Special Funds (2013KJCX0036) http://www.gdhed.edu.cn/; Science and Technology Supporting Project of Xinjiang Uygur Autonomous Region (2013911122) http://www.most.gov.cn/index.htm; all of these support Institute of Molecular Immunology and Li Ma is the recipient. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.