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. 2014 Dec;21(12):1635-44.
doi: 10.1128/CVI.00499-14. Epub 2014 Oct 1.

IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment

Qianting Yang  1 , Yi Cai  1 , Wei Zhao  1 , Fan Wu  1 , Mingxia Zhang  1 , Kai Luo  1 , Yan Zhang  2 , Haiying Liu  2 , Boping Zhou  3 , Hardy Kornfeld  4 , Xinchun Chen  5
Affiliations

IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment

Qianting Yang et al. Clin Vaccine Immunol. 2014 Dec.

Abstract

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins.

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Figures

FIG 1
FIG 1
Differential plasma cytokine/chemokine expression patterns between LTBI and TB. (A) The levels of 26 cytokines/chemokines in plasma were detected by Luminex assay. The comparison index was calculated by dividing the mean plasma level of each cytokine/chemokine for PTB (n = 20) by that for LTBI (n = 17). The nonparametric Mann-Whitney U test was used to compare the differences between groups. *, P < 0.002. (B) The plasma levels of G-CSF, IP-10/CXCL10, and MIG/CXCL9 in PTB (n = 20) and LTBI (n = 17) subjects were significantly different. Each dot represents one individual; horizontal lines and error bars represent mean values ± standard errors of the means (SEM). The nonparametric Mann-Whitney U test was used to compare the differences between groups. P values are indicated.
FIG 2
FIG 2
Characterization of cytokine and chemokine expression in TBP and non-TBP patients. (A) The levels of TNF-α, IL-6, IL-13, MCP-1, IL-8, IL-10, MIG, and IP-10 in plasmas and paired pleural fluid samples from TBP patients (n = 10) were determined by Luminex assay. The paired t test was used for comparison, and P values are indicated. (B) The levels of 26 cytokines/chemokines in pleural fluid were detected by Luminex assay. The comparison index was calculated by dividing the mean level of each cytokine/chemokine in pleural fluid from TBP patients (n = 51) by that for non-TBP patients (n = 36). The nonparametric Mann-Whitney U test was used to compare the differences between groups. *, P < 0.002.
FIG 3
FIG 3
Expression of IP-10, MIG, and IL-10 in CSF from TBM and non-TBM patients. (A) The levels of IP-10, MIG, and IL-10 in CSF from TBM (n = 16) and non-TBM (n = 40) patients were determined by Luminex assay. Each dot represents one individual; horizontal lines and error bars represent mean values ± SEM. The nonparametric Mann-Whitney U test was used to compare the differences between groups. P values are indicated. (B) ROC curves analyzing the diagnostic values of IP-10, MIG, and IL-10 in CSF for discriminating TBM and non-TBM.
FIG 4
FIG 4
Dynamic changes of cytokine/chemokine expression in plasma before and after anti-TB treatment. (A) The levels of eotaxin-1, IP-10, G-CSF, IFN-γ, MCP-1, and MIG in the plasmas of PTB patients (n = 8) before anti-TB treatment and 3, 6, and 12 months after initiation of anti-TB treatment were detected by Luminex assay. (B) The MCP-1/IP-10, MCP-1/MIG, eotaxin-1/IP-10, and eotaxin-1/MIG ratios in plasmas of PTB patients (n = 8) before anti-TB treatment and 3, 6, and 12 months after initiation of anti-TB treatment were calculated. The paired t test was used for comparison between different times points, and P values are indicated. *, P < 0.05; **, P < 0.005. 0m, before anti-TB treatment; 3m, 3 months after initiation of anti-TB treatment; 6m, 6 months after initiation of anti-TB treatment; 12m, 12 months after initiation of anti-TB treatment.
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References

    1. Dorman SE. 2010. New diagnostic tests for tuberculosis: bench, bedside, and beyond. Clin. Infect. Dis. 50(Suppl 3):S173–S177. 10.1086/651488. - DOI - PubMed
    1. Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, Dye C. 2003. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch. Intern. Med. 163:1009–1021. 10.1001/archinte.163.9.1009. - DOI - PubMed
    1. Shenai S, Amisano D, Ronacher K, Kriel M, Banada PP, Song T, Lee M, Joh JS, Winter J, Thayer R, Via LE, Kim S, Barry CE, 3rd, Walzl G, Alland D. 2013. Exploring alternative biomaterials for diagnosis of pulmonary tuberculosis in HIV-negative patients by use of the GeneXpert MTB/RIF assay. J. Clin. Microbiol. 51:4161–4166. 10.1128/JCM.01743-13. - DOI - PMC - PubMed
    1. Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. 2014. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst. Rev. 1:CD009593. 10.1002/14651858.CD009593.pub3. - DOI - PMC - PubMed
    1. Kim CH, Woo H, Hyun IG, Kim C, Choi JH, Jang SH, Park SM, Kim DG, Lee MG, Jung KS, Hyun J, Kim HS. 2014. A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice. J. Thorac. Dis. 6:625–631. 10.3978/j.issn.2072-1439.2014.04.12. - DOI - PMC - PubMed

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