Differential Expression of Activation Markers by Mycobacterium tuberculosis-specific CD4+ T Cell Distinguishes Extrapulmonary From Pulmonary Tuberculosis and Latent Infection.

Autor: Silveira-Mattos PS; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil., Barreto-Duarte B; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Universidade Salvador, Laureate Universities, Salvador, Bahia, Brazil., Vasconcelos B; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil., Fukutani KF; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil., Vinhaes CL; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil., Oliveira-De-Souza D; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil., Ibegbu CC; Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.; Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Figueiredo MC; Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Sterling TR; Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA., Rengarajan J; Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.; Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Andrade BB; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil.; Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil.; Universidade Salvador, Laureate Universities, Salvador, Bahia, Brazil.; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil.; Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2020 Nov 05; Vol. 71 (8), pp. 1905-1911.
DOI: 10.1093/cid/ciz1070
Abstrakt: Background: Diagnosis of active tuberculosis (ATB) currently relies on detection of Mycobacterium 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.
Methods: 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 human immunodeficiency virus (HIV) coinfection on diagnostic performance. Frequencies of interferon-γ +CD4+T cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry.
Results: EPTB and PTB were associated with higher frequencies of CD4+T cells expressing CD38, HLADR, or Ki67 compared with LTBI (all P values < .001). Moreover, frequencies of HLADR+ (P = .03) or Ki67+ (P < .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.
Conclusions: 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.
(© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE