Regulation network of serum cytokines induced by tuberculosis-specific antigens reveals biomarkers for tuberculosis diagnosis

Wei, M; Wu, Zhi‐Yong; Lin, Jin-Fei; Li, Y; Qian, Zhida; Xie, Yujia; Su, Hongwei; Zhou, Wanding

doi:10.4238/2015.december.16.18

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…In agreement with previous reports, TNF‐α and IL‐8 levels were increased in TB patients. In fact, these mycobacterial‐specific cytokines have been proposed for use in immunodiagnostics . Interestingly, our data lend support to the theory that TB patients have a Th1/Th2 imbalance that is characterized by high IL‐4 but low IFN‐γ levels, a phenomenon that is a significant factor in the pathogenesis and development of TB .…”

Section: Discussionsupporting

confidence: 81%

“…In fact, these mycobacterial-specific cytokines have been proposed for use in immunodiagnostics. 35,36 Interestingly, our data lend support to the theory that TB patients have a Th1/ Th2 imbalance that is characterized by high IL-4 but low IFN-γ levels, a phenomenon that is a significant factor in the pathogenesis and development of TB. 37,38 It is possible that this Th1/Th2 balance shift plays a role in the high cytotoxic background of CD8 + T cells.…”

Section: Discussionsupporting

confidence: 73%

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Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Chávez‐Galán

Illescas‐Eugenio

Álvarez-Sekely

et al. 2019

Microbiology and Immunology

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major cause of morbidity and mortality worldwide. In the host's immune response system, T cells play a critical role in mediating protection against Mtb infection, but the role of CD8+ T cells is still controversial. We evaluated the phenotypical characterization and cytotoxic ability of CD8+ T cells by flow cytometry‐based assay. Cytokine levels in serum were measured by multiplex cytokine assay. Our data show that cells from TB patients have an increased percentage of peripheral blood CD8+αβ+ T (p = 0.02) and CD56+CD8+ T (p = 0.02) and a decreased frequency of NKG2D+CD8+ T (p = 0.02) compared with healthy donors. Unlike CD8+ T cells from healthy donors, CD8+ T cells from TB patients exhibit greater cytotoxicity, mediated by HLA class I molecules, on autologous monocytes in the presence of mycobacterial antigens (p = 0.005). Finally, TB patients have a proinflammatory profile characterized by serum high level of TNF‐α (p = 0.02) and IL‐8 (p = 0.0001), but, interestingly, IL‐4 (p = 0.002) was also increased compared with healthy donors. Our data show evidence regarding the highly cytotoxic status of CD8+ T cells in Mtb infection. These cytotoxic cells restricted to HLA‐A, B, and C could be used to optimize strategies for designing new TB vaccines or for identifying markers of disease progression.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 73%

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Chávez‐Galán

Illescas‐Eugenio

Álvarez-Sekely

et al. 2019

Microbiology and Immunology

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“…Studies have also reported that IL-7 has been involved in regulating naive T cell homeostasis [41]. Previously published data reports that IL-7 is elevated in patients with tuberculosis compared to latent TB or healthy controls [42, 43], but in contrast other studies report that IL-7 response to stimulation with TB antigen displayed diminished cytokine levels compared to healthy controls [44]. Similar to the latter results, our data also show that IL-7 exhibits decreased levels in PTB compared to LTB or NTB at homeostasis or upon TB antigen stimulation and levels were significantly restored after successful completion of anti-TB treatment.…”

Section: Discussionmentioning

confidence: 99%

Diminished plasma levels of common γ-chain cytokines in pulmonary tuberculosis and reversal following treatment

et al. 2017

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BackgroundThe immune response to tuberculosis (TB) is T cell dependent. T cells are the major facilitators of protection and effector functions with CD4+ T cells being the most important players, followed by CD8+ T cells. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 play a vital role in peripheral T cell growth and survival. However, the role of common γ-chain cytokines in pulmonary TB (PTB) is poorly understood.Aim and methodsTo examine the association of circulating common γ-chain cytokines with TB disease or infection, we examined the systemic levels of IL-2, IL-7, IL-15, and IL-21 in individuals with PTB, latent TB (LTB) or no TB infection (NTB). We also examined the levels of these cytokines in PTB individuals before and after anti-tuberculosis treatment.ResultsCirculating levels of IL-2, IL-7 and IL-21 were significantly diminished in PTB compared to LTB or NTB individuals. Moreover, TB antigen stimulated whole blood also exhibited diminished levels of common γ-chain cytokines in PTB compared to LTB or NTB individuals. The plasma levels of common γ-chain cytokines exhibited no significant association with the severity or extent of TB disease or with bacterial burdens. However, upon standard anti-TB treatment, both the systemic as well as the TB antigen stimulated levels of IL-2, IL-7 and IL-21 were significantly increased in PTB individuals.ConclusionTherefore our data demonstrate that diminished levels of common γ-chain cytokines are a common characteristic of PTB and potentially highlight the importance of boosting these responses to improve treatment outcomes.

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“…The proportion of BCG vaccination was similar among the groups with LTBI, active TB, and noninfected individuals. Seven papers [26,28,36,38,[42][43][44] compared the statistical difference between those with and without vaccination, and only two reported statistical significance [45,20], having a lower percentage in the active TB group compared to healthy controls (healthy persons with no known risk of TB exposure), TB-exposed persons with QFT-negative results, and people with LTBI. One article reported no significant associations between levels of cytokines and BCG scar [21], and one included BCG status in the multinomial regression model getting an adjusted odds ratio increased for TNF-α and IL-6 [22].…”

Section: Participantsmentioning

confidence: 99%

“…Only 4 of the reports took into account the study origin and population's ethnicity as a confounding factor, and these were evaluated by self-reported ethnicity [28,38,48,52].…”

Section: Journal Of Immunology Researchmentioning

confidence: 99%

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

Herrera

Vera

Keynan

et al. 2020

Journal of Immunology Research

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Background. Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective. To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods. We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants’ information, diagnostic criteria, IP, detection methods, and biases were collected. Results. We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions. It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.

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Regulation network of serum cytokines induced by tuberculosis-specific antigens reveals biomarkers for tuberculosis diagnosis

Cited by 18 publications

References 28 publications

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Diminished plasma levels of common γ-chain cytokines in pulmonary tuberculosis and reversal following treatment

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

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Regulation network of serum cytokines induced by tuberculosis-specific antigens reveals biomarkers for tuberculosis diagnosis

Cited by 18 publications

References 28 publications

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential

Diminished plasma levels of common γ-chain cytokines in pulmonary tuberculosis and reversal following treatment

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

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Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential