Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection. Silveira-Mattos, P. S, Barreto-Duarte, B., Vasconcelos, B., Fukutani, K. F, Vinhaes, C. L, Oliveira-de-Souza, D., Ibegbu, C. C, Figueiredo, M. C, Sterling, T. R, Rengarajan, J., & Andrade, B. B Clinical Infectious Diseases, 71(8):1905–1911, 2020.
Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection [link]Paper  doi  abstract   bibtex   
Diagnosis of active tuberculosis (ATB) currently relies on detection of M. tuberculosis (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis of both EPTB and pulmonary TB (PTB), and timely initiation of anti-TB therapy.A case-control study was performed using discriminant analyses to validate an approach using Mtb-specific CD4+T-cell activation markers in blood to discriminate PTB and EPTB from latent TB infection (LTBI) as well as EPTB from PTB in 270 Brazilian individuals. We further tested the effect of HIV co-infection on diagnostic performance. Frequencies of IFN$γ$+CD4+T-cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry.EPTB and PTB were associated with higher frequencies of CD4+T-cells expressing CD38, HLADR or Ki67 compared to LTBI (all p-values $\$$\$\textless .001). Moreover, frequencies of HLADR+ (p= .03) or Ki67+ (p$\$$\$\textless .001) cells accurately distinguished EPTB from PTB. HIV infection did not affect the capacity of these markers to distinguish ATB from LTBI or EPTB from PTB.Cell activation markers in Mtb-specific CD4+T-cells distinguished ATB from LTBI, and EPTB from PTB, regardless of HIV infection status. These parameters provide an attractive approach for developing blood-based diagnostic tests for both active and latent TB.
@article{10.1093/cid/ciz1070,
abstract = {Diagnosis of active tuberculosis (ATB) currently relies on detection of M. tuberculosis (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis of both EPTB and pulmonary TB (PTB), and timely initiation of anti-TB therapy.A case-control study was performed using discriminant analyses to validate an approach using Mtb-specific CD4+T-cell activation markers in blood to discriminate PTB and EPTB from latent TB infection (LTBI) as well as EPTB from PTB in 270 Brazilian individuals. We further tested the effect of HIV co-infection on diagnostic performance. Frequencies of IFN$\gamma$+CD4+T-cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry.EPTB and PTB were associated with higher frequencies of CD4+T-cells expressing CD38, HLADR or Ki67 compared to LTBI (all p-values $\backslash$$\backslash${\textless} .001). Moreover, frequencies of HLADR+ (p= .03) or Ki67+ (p$\backslash$$\backslash${\textless} .001) cells accurately distinguished EPTB from PTB. HIV infection did not affect the capacity of these markers to distinguish ATB from LTBI or EPTB from PTB.Cell activation markers in Mtb-specific CD4+T-cells distinguished ATB from LTBI, and EPTB from PTB, regardless of HIV infection status. These parameters provide an attractive approach for developing blood-based diagnostic tests for both active and latent TB.},
annote = {ciz1070},
author = {Silveira-Mattos, Paulo S and Barreto-Duarte, Beatriz and Vasconcelos, Beatriz and Fukutani, Kiyoshi F and Vinhaes, Caian L and Oliveira-de-Souza, Deivide and Ibegbu, Chris C and Figueiredo, Marina C and Sterling, Timothy R and Rengarajan, Jyothi and Andrade, Bruno B},
doi = {10.1093/cid/ciz1070},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Silveira-Mattos et al. - 2020 - Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4 T-cell distingu.pdf:pdf},
issn = {1058-4838},
journal = {Clinical Infectious Diseases},
keywords = {fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
number = {8},
pages = {1905--1911},
pmid = {31665254},
title = {{Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection}},
url = {https://doi.org/10.1093/cid/ciz1070},
volume = {71},
year = {2020}
}

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