| Author | Mattos, Paulo Sérgio de Morais da Silveira | |
| Author | Duarte, Beatriz Barreto | |
| Author | Vasconcelos, Beatriz | |
| Author | Fukutani, Kiyoshi Ferreira | |
| Author | Vinhaes, Caian Leal | |
| Author | Souza, Deivide Oliveira de | |
| Author | Ibegbu, Chris C. | |
| Author | Figueiredo, Marina C. | |
| Author | Sterling, Timothy R. | |
| Author | Rengarajan, Jyothi | |
| Author | Andrade, Bruno de Bezerril | |
| Access date | 2019-11-18T17:25:06Z | |
| Available date | 2019-11-18T17:25:06Z | |
| Document date | 2019 | |
| Citation | MATTOS, Paulo Sérgio de Morais da Silveira et al. Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection. Clinical Infectious Diseases, p. 1-23, 2019. | |
| ISSN | 1058-4838 | |
| URI | https://www.arca.fiocruz.br/handle/icict/37131 | |
| Sponsorship | Intramural Research Program of the Fundação Oswaldo Cruz, Departamento de Ciência e Tecnologia (DECIT) - Secretaria de Ciência e Tecnologia (SCTIE) – Ministério da Saúde (MS), Brazil [25029.000507/2013-07] and the National Institutes of Allergy and Infectious Diseases [U01-AI069923]. PSSM and DOS received scholarship from Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). The work of BBA was supported by grants from NIH (U01AI115940, U01AI069923). BBA is a senior scientist from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). | |
| Language | eng | en_US |
| Rights | restricted access | |
| Subject in Portuguese | Tuberculose | pt_BR |
| Subject in Portuguese | Biomarcadores | pt_BR |
| Subject in Portuguese | TB extrapulmonar | pt_BR |
| Subject in Portuguese | Células T | pt_BR |
| Subject in Portuguese | Ativação imune | pt_BR |
| Title | Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection | en_US |
| Type | Preprint | |
| DOI | 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. 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 HIV co-infection on diagnostic performance. Frequencies of IFNγ+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 to 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. Conclusion: 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil. | |
| Affilliation | Emory University School of Medicine. Emory Vaccine Center. Atlanta, Georgia, USA / Emory University School of Medicine. Department of Medicine. Division of Infectious Disease. Atlanta, Georgia, USA. | |
| Affilliation | Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA. | |
| Affilliation | Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA. | |
| Affilliation | Emory University School of Medicine. Emory Vaccine Center. Atlanta, Georgia, USA / Emory University School of Medicine. Department of Medicine. Division of Infectious Disease. Atlanta, Georgia, USA. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, TN, USA / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa. | |
| Subject | Tuberculosis | en_US |
| Subject | Biomarkers | en_US |
| Subject | Extrapulmonary TB | en_US |
| Subject | T-cells | en_US |
| Subject | Immune activation | en_US |
